- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03449251
A Series of Pilot Studies to Evaluate the haemoDynamic and mEtabolic Effects oF apelIn aNd rElaxin (DEFINE)
A Series of Pilot Studies to Evaluate the Haemodynamic and Metabolic Effects of Apelin and Relaxin in Healthy Humans, Subjects With Increased Weight and Patients With Type 2 Diabetes Mellitus
Type two diabetes mellitus (T2DM) is a common, long term metabolic disorder characterised by hyperglycaemia (high blood glucose) resulting from insulin resistance and relative insulin insufficiency. The risk of developing insulin resistance and subsequently T2DM is increased by being overweight and also through a sedentary lifestyle. As the onset can be gradual, physiological damage may have occurred prior to diagnosis. Diabetes is associated with the development of microvascular complications (diabetic nephropathy, neuropathy, and retinopathy), and macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke). While there are many treatments available for T2DM, these complications may still arise, leading to significant morbidity and mortality. There is therefore an urgent need to identify novel signalling pathways that may contribute to the development of diabetes related complications. The identification of these pathways may ultimately lead to the development of new therapies targeting better blood glucose control and preventing these subsequent complications.
Both animal and human studies have indicated that two endogenous peptides, apelin and relaxin both act as vasodilators in the human cardiovascular system and could also have beneficial action in T2DM. Therefore, we aim to carry out experimental medicine studies to test this hypothesis, and explore the signalling pathway in the human vascular system.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
An extensive body of evidence demonstrates a direct association between T2DM and cardiovascular complications and mortality. Unfortunately, current therapies for diabetes have failed to be translated into improvements in cardiovascular outcomes, highlighting an urgent need to develop novel therapeutic strategies that can ultimately achieve the dual outcome of improving glycaemic control and improving cardiovascular function.
While the precise cellular mechanisms involved remain to be elucidated, we hypothesise that the apelin and relaxin pathways meet these two criteria and therefore are potential therapeutic targets in conditions of abnormal glucose metabolism and heart failure.
Apelin and relaxin are safe for parenteral use as they are naturally occurring peptide hormones, have a short half-life and will be rapidly cleared. They target endogenous receptors and post-receptor signalling, and have been used in human trials without any significant side effects reported.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Cambridgeshire
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Cambridge, Cambridgeshire, United Kingdom, CB20QQ
- Addenbrooke's Hospital
-
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Healthy participants
- Have given written informed consent to participate
- Aged 18 to 70 years inclusive
- Male or female
- Current non-smoker
- If female, either postmenopausal or on days 2-9 of menstrual cycle and negative pregnancy test performed on the day of the of visit
- BMI in range for studies 1 and 4: 18.5-24.9 kg/m2 with waist circumference lower than 88 centimetres (35 inches) for women or 102 cm (40 inches) for men, and/or body fat level less than 32 % for women or 25% for men
- BMI in range for studies 2 and 3: 18.5-30.0 kg/m2 without limitations in waist circumference or body fat level
Overweight/obese participants
- Have given written informed consent to participate
- Aged 18 to 70 years inclusive
- Male or female
- Current non-smoker
- If female, either postmenopausal or on days 2-9 of menstrual cycle and negative pregnancy test performed on the day of the of visit
- BMI in range of 25-34.9 kg/m2 (inclusive) with either waist circumference higher than 88cm (35 inches) for women or 102 cm (40 inches) for men, and/or body fat levels in excess of 32% for women or 25% for men
Participants with type 2 diabetes mellitus
- Have given written informed consent to participate
- Aged 18 to 70 years inclusive
- Male or female
- Current non-smoker
- If female, either postmenopausal or on days 2-9 of menstrual cycle and negative pregnancy test performed on the day of the of visit
- BMI in range of 25-34.9 kg/m2 (inclusive) with either waist circumference higher than 88cm (35 inches) for women or 102 cm (40 inches) for men, and/or body fat levels in excess of 32% for women or 25% for men
- Documented diagnosis of Type 2 Diabetes Mellitus, either diet controlled or treated with oral hypoglycaemic therapy
Exclusion Criteria:
- Hypersensitivity to any of the study drugs or excipients
- Systemic Hypertension (sustained BP >160/100mmHg) or hypotension (systolic BP below 90 mmHg)
- Known heart disease
- Implanted heart pace-maker or implantable cardioverter defibrillator (ICD)
- Known active malignancy
- Known renal failure (creatinine >140µmol/L)
- Known neurological disease
- History of Scleroderma (Study 4 only)
- Current pregnancy, breast feeding
- Use of vasoactive medications or NSAIDS/aspirin within 24 hours of study visits
- Use of caffeine within 24 hours of study visits
- Current involvement in the active treatment phase of other research studies, (excluding observations/non-interventional)
- Second or third-degree AV block, sino-atrial block, sick sinus syndrome or sinus bradycardia
- Known HIV, hepatitis B or C
- Needle phobia
- Participants treated with formal anticoagulant therapy such as, but not limited to, heparin, warfarin or clopidogrel
- Diagnosis of Type 1 Diabetes Mellitus or current usage of insulin or other injectable drugs for the treatment of diabetes such as but not limited to GLP1 agonists
- BMI <18.5
- Aged <18 or >70 years
- Any other clinical reason which may preclude entry in the opinion of the investigator
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Substudy 1A - Apelin
In sub-study 1A Healthy participants will receive systemic infusions of Apelin to establish a dose range
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Apelin is an endogenous peptide that activate a single G-protein couple receptor.
Apelin inhibits insulin secretion, decreases glucose levels and increases insulin sensitivity.
|
Experimental: Substudy 1B - Apelin/Normal Saline
In sub-study 1B , individuals with Type 2 Diabetes and individuals with increase weight will receive systemic infusions of Apelin or Normal Saline
|
Apelin is an endogenous peptide that activate a single G-protein couple receptor.
Apelin inhibits insulin secretion, decreases glucose levels and increases insulin sensitivity.
Vehicle
Other Names:
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Experimental: Substudy 2A - Relaxin/Normal Saline
In sub-study 2A Healthy participants will receive intra-arterial infusions of Relaxin
|
Vehicle
Other Names:
Relaxin is RLN2 encoded endogenous peptide hormone, which binds to G protein coupled receptor RXFP1.
Other Names:
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Experimental: Substudy 2B - Relaxin
In sub-study 2B Healthy participants will receive intra-arterial infusions of Relaxin followed by verapamil (on a background infusion of either LN Monomethyl Arginine or Normal Saline, to test effects on nitric oxide)
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Relaxin is RLN2 encoded endogenous peptide hormone, which binds to G protein coupled receptor RXFP1.
Other Names:
NO independent challenge agent
Basal NO synthase inhibitor
Other Names:
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Experimental: Substudy 3A - Relaxin with Apelin/Saline
In sub-study 3A Healthy participants will receive intra-arterial infusions of Relaxin (background infusion apelin/Normal Saline)
|
Apelin is an endogenous peptide that activate a single G-protein couple receptor.
Apelin inhibits insulin secretion, decreases glucose levels and increases insulin sensitivity.
Vehicle
Other Names:
Relaxin is RLN2 encoded endogenous peptide hormone, which binds to G protein coupled receptor RXFP1.
Other Names:
|
Experimental: Substudy 3B - Apelin with Relaxin/Saline
In sub-study 3B Healthy participants will receive intra-arterial infusions of Apelin (background infusion Relaxin/Normal Saline)
|
Apelin is an endogenous peptide that activate a single G-protein couple receptor.
Apelin inhibits insulin secretion, decreases glucose levels and increases insulin sensitivity.
Vehicle
Other Names:
Relaxin is RLN2 encoded endogenous peptide hormone, which binds to G protein coupled receptor RXFP1.
Other Names:
|
Experimental: Substudy 4 - Apelin and Relaxin
In sub-study 4 Healthy participants, Individuals with Type 2 Diabetes and Individuals with increase weight will receive systemic infusions of Normal saline, Relaxin, Apelin and relaxin
|
Apelin is an endogenous peptide that activate a single G-protein couple receptor.
Apelin inhibits insulin secretion, decreases glucose levels and increases insulin sensitivity.
Relaxin is RLN2 encoded endogenous peptide hormone, which binds to G protein coupled receptor RXFP1.
Other Names:
|
Experimental: Substudy 5 - Relaxin/Saline
In sub-study 5 Healthy participants will be allocated to 1 of 4 Relaxin dosing groups and will receive dorsal hand vein infusion of 3 incremental doses of Normal Saline/ D5W and Relaxin
|
Vehicle
Other Names:
Relaxin is RLN2 encoded endogenous peptide hormone, which binds to G protein coupled receptor RXFP1.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sub-study 1a: Changes in markers of glucose homeostasis in healthy participants after infusion of apelin (Glucose)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Glucose, in mmol/l
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1a: Changes in markers of glucose homeostasis in healthy participants after infusion of apelin (C-Peptide)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
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C-peptide, in pmol/L
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1a: Changes in markers of glucose homeostasis in healthy participants after infusion of apelin (Glucagon)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Glucagon, in pg/ml
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1a: Changes in markers of glucose homeostasis in healthy participants after infusion of apelin (Insulin)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Insulin, in pmol/L
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1a: Changes in markers of glucose homeostasis in healthy participants after infusion of apelin (TNF-alpha)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
TNF-alpha, in pg/ml
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1b: Changes in markers of glucose homeostasis in participants with increased weight and participants with type 2 diabetes mellitus after infusion of apelin with or without mixed meal tolerance in obese/overweight and T2DM participants
Time Frame: Visit 2 to visit 5, over a period of up to 14 weeks
|
Glucose, in mmol/l
|
Visit 2 to visit 5, over a period of up to 14 weeks
|
Sub-study 1b: Changes in markers of glucose homeostasis in participants with increased weight and participants with type 2 diabetes mellitus after infusion of apelin with or without mixed meal tolerance in obese/overweight and T2DM participants
Time Frame: Visit 2 to visit 5, over a period of up to 14 weeks
|
C-peptide, in pmol/L
|
Visit 2 to visit 5, over a period of up to 14 weeks
|
Sub-study 1b: Changes in markers of glucose homeostasis in participants with increased weight and participants with type 2 diabetes mellitus after infusion of apelin with or without mixed meal tolerance in obese/overweight and T2DM participants
Time Frame: Visit 2 to visit 5, over a period of up to 14 weeks
|
Glucagon, in pg/ml
|
Visit 2 to visit 5, over a period of up to 14 weeks
|
Sub-study 1b: Changes in markers of glucose homeostasis in participants with increased weight and participants with type 2 diabetes mellitus after infusion of apelin with or without mixed meal tolerance in obese/overweight and T2DM participants
Time Frame: Visit 2 to visit 5, over a period of up to 14 weeks
|
Insulin, in pmol/L
|
Visit 2 to visit 5, over a period of up to 14 weeks
|
Sub-study 1b: Changes in markers of glucose homeostasis in participants with increased weight and participants with type 2 diabetes mellitus after infusion of apelin with or without mixed meal tolerance in obese/overweight and T2DM participants
Time Frame: Visit 2 to visit 5, over a period of up to 14 weeks
|
TNF-alpha, in pg/ml
|
Visit 2 to visit 5, over a period of up to 14 weeks
|
Sub-study 2a: Change in forearm blood flow parameters in healthy participants after infusion of relaxin (Absolute Flow)
Time Frame: Within visit 2, over a period of up to 4 weeks
|
Absolute flow in the infused arm, in mg/dL/min
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Within visit 2, over a period of up to 4 weeks
|
Sub-study 2a: Change in forearm blood flow parameters in healthy participants after infusion of relaxin (Percentage Change)
Time Frame: Within visit 2, over a period of up to 4 weeks
|
Percentage change in the infused arm, in %
|
Within visit 2, over a period of up to 4 weeks
|
Sub-study 2a: Change in forearm blood flow parameters in healthy participants after infusion of relaxin (Ratio)
Time Frame: Within visit 2, over a period of up to 4 weeks
|
Ratio, expressed as a number (no units as this is a ratio)
|
Within visit 2, over a period of up to 4 weeks
|
Sub-study 2b: Change in forearm blood flow parameters in healthy participants after infusion of relaxin in the presence of L-NMMA or normal saline
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Ratio; absolute flow and percentage change in the infused arm
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-study 2b: Change in forearm blood flow parameters in health participants after infusion of verapamil in the presence of L-NMMA or normal saline (Ratio)
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Ratio; expressed as a number (no units as this is a ratio)
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-study 2b: Change in forearm blood flow parameters in health participants after infusion of verapamil in the presence of L-NMMA or normal saline (Absolute Flow)
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Absolute flow in the infused arm, in mg/dL/min
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-study 2b: Change in forearm blood flow parameters in health participants after infusion of verapamil in the presence of L-NMMA or normal saline (Percentage Change)
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Percentage change in the infused arm, In %
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-Study 3a: Change in forearm blood flow parameters in healthy participants after incremental infusions of intra-arterial relaxin in the presence of apelin
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Ratio; absolute flow and percentage change in the infused arm
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-Study 3a: Change in forearm blood flow parameters in healthy participants after incremental infusions of intra-arterial relaxin in the presence of apelin (Ratio)
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Ratio, expressed as a number (no units as this is a ratio)
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-Study 3a: Change in forearm blood flow parameters in healthy participants after incremental infusions of intra-arterial relaxin in the presence of apelin (Absolute Flow)
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Absolute flow in the infused arm, in mg/dL/min
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-Study 3a: Change in forearm blood flow parameters in healthy participants after incremental infusions of intra-arterial relaxin in the presence of apelin (Percentage Change)
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Percentage change in the infused arm, In %
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-Study 3b: Change in forearm blood flow parameters in healthy participants after incremental infusions of intra-arterial apelin in the presence of relaxin (Ratio)
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Ratio, expressed as a number (no units as this is a ratio)
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-Study 3b: Change in forearm blood flow parameters in healthy participants after incremental infusions of intra-arterial apelin in the presence of relaxin (Absolute Flow)
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Absolute flow in the infused arm, in mg/dL/min
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-Study 3b: Change in forearm blood flow parameters in healthy participants after incremental infusions of intra-arterial apelin in the presence of relaxin (Percentage Change)
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Percentage change in the infused arm, In %
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-study 4: Changes in markers of glucose homeostasis healthy participants, participants with increased weight and participants with type 2 diabetes mellitus after infusion of relaxin with and without apelin (Glucose)
Time Frame: Visit 2 to Visit 4, over a period of up to 8 weeks
|
Glucose, in each of the groups, in mmol/L
|
Visit 2 to Visit 4, over a period of up to 8 weeks
|
Sub-study 4: Changes in markers of glucose homeostasis healthy participants, participants with increased weight and participants with type 2 diabetes mellitus after infusion of relaxin with and without apelin (C-peptide)
Time Frame: Visit 2 to Visit 4, over a period of up to 8 weeks
|
C-peptide, in each of the groups, in pmol/L
|
Visit 2 to Visit 4, over a period of up to 8 weeks
|
Sub-study 4: Changes in markers of glucose homeostasis healthy participants, participants with increased weight and participants with type 2 diabetes mellitus after infusion of relaxin with and without apelin (Glucagon)
Time Frame: Visit 2 to Visit 4, over a period of up to 8 weeks
|
glucagon, in each of the groups,in pg/ml
|
Visit 2 to Visit 4, over a period of up to 8 weeks
|
Sub-study 4: Changes in markers of glucose homeostasis healthy participants, participants with increased weight and participants with type 2 diabetes mellitus after infusion of relaxin with and without apelin (Insulin)
Time Frame: Visit 2 to Visit 4, over a period of up to 8 weeks
|
Insulin, in each of the groups, in pmol/L
|
Visit 2 to Visit 4, over a period of up to 8 weeks
|
Sub-study 4: Changes in markers of glucose homeostasis healthy participants, participants with increased weight and participants with type 2 diabetes mellitus after infusion of relaxin with and without apelin (TNF-alpha)
Time Frame: Visit 2 to Visit 4, over a period of up to 8 weeks
|
TNF-alpha, in each of the groups, in pg/ml
|
Visit 2 to Visit 4, over a period of up to 8 weeks
|
Sub-study 5: Change in hand vein diameter after relaxin infusion in healthy participants
Time Frame: Visit 2
|
Hand vein Demeter is measured using Aellig dorsal hand vein technique
|
Visit 2
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sub-study 1a: Changes in parameters of cardiovascular haemodynamics in healthy participants after infusion of apelin (Echocardiography)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by Echocardiography, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1a: Changes in parameters of cardiovascular haemodynamics in healthy participants after infusion of apelin (Innocor)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by Innocor, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1a: Changes in parameters of cardiovascular haemodynamics in healthy participants after infusion of apelin (Bioimpedance)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by bioimpedance, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1b: Changes in parameters of cardiovascular haemodynamics in obese/overweight and T2DM participants after infusion of apelin (Echocardiography)
Time Frame: VIsit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by Echocardiography, in L/min
|
VIsit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1b: Changes in parameters of cardiovascular haemodynamics in obese/overweight and T2DM participants after infusion of apelin (Innocor)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by Innocor, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1b: Changes in parameters of cardiovascular haemodynamics in obese/overweight and T2DM participants after infusion of apelin (Bioimpedance)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by bioimpedance, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1b: Changes in parameters of cardiovascular haemodynamics in obese/overweight and T2DM participants after infusion of apelin,after a mixed meal challenge (Echocardiography)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by Echocardiography, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1b: Changes in parameters of cardiovascular haemodynamics in obese/overweight and T2DM participants after infusion of apelin, after a mixed meal challenge (Innocor)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by Innocor, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1b: Changes in parameters of cardiovascular haemodynamics in obese/overweight and T2DM participants after infusion of apelin,after a mixed meal challenge (Bioimpedance)
Time Frame: VIsit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by bioimpedance, in L/min
|
VIsit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 1b: Changes in markers of glucose homeostasis after infusion of apelin in obese/overweight and T2DM, after a mixed meal challenge (Clugose)
Time Frame: Visit 2 to visit 5, over a period of up to 14 weeks
|
Glucose, in mmol/L
|
Visit 2 to visit 5, over a period of up to 14 weeks
|
Sub-study 1b: Changes in markers of glucose homeostasis after infusion of apelin in obese/overweight and T2DM, after a mixed meal challenge (C-peptide)
Time Frame: Visit 2 to visit 5, over a period of up to 14 weeks
|
C-peptide, in pmol/L
|
Visit 2 to visit 5, over a period of up to 14 weeks
|
Sub-study 1b: Changes in markers of glucose homeostasis after infusion of apelin in obese/overweight and T2DM, after a mixed meal challenge (Glucagon)
Time Frame: Visit 2 to visit 5, over a period of up to 14 weeks
|
Glucagon, in pg/ml
|
Visit 2 to visit 5, over a period of up to 14 weeks
|
Sub-study 1b: Changes in markers of glucose homeostasis after infusion of apelin in obese/overweight and T2DM, after a mixed meal challenge (Insulin)
Time Frame: Visit 2 to visit 5, over a period of up to 14 weeks
|
Insulin, in pmol/L
|
Visit 2 to visit 5, over a period of up to 14 weeks
|
Sub-study 1b: Changes in markers of glucose homeostasis after infusion of apelin in obese/overweight and T2DM, after a mixed meal challenge (TNF alpha)
Time Frame: Visit 2 to visit 5, over a period of up to 14 weeks
|
TNF alpha, in pg/ml
|
Visit 2 to visit 5, over a period of up to 14 weeks
|
Sub-study 2b: Change in forearm blood flow parameters after infusion of verapamil in the presence of L-NMMA or saline (Ratio)
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Ratio,expressed as a number (no units as this is a ratio)
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-study 2b: Change in forearm blood flow parameters after infusion of verapamil in the presence of L-NMMA or saline (Absolute Flow)
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Absolute flow in the infused arm, in mg/dL/min
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-study 2b: Change in forearm blood flow parameters after infusion of verapamil in the presence of L-NMMA or saline (Percentage Change)
Time Frame: Visit 2 to visit 3, over a period of up to 10 weeks
|
Percentage change in the infused arm, In %
|
Visit 2 to visit 3, over a period of up to 10 weeks
|
Sub-study 4: Change in cardiovascular haemodynamics after infusion of relaxin (Echocardiography)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by Echocardiography, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 4: Change in cardiovascular haemodynamics after infusion of relaxin (Bioimpedance)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by bioimpedance, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 4: Change in cardiovascular haemodynamics after infusion of relaxin (Innocor)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by Innocor, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 4: Change in cardiovascular haemodynamics after combined infusion of relaxin and apelin (Echocardiography)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by Echocardiography, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 4: Change in cardiovascular haemodynamics after combined infusion of relaxin and apelin (Bioimpedance)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by bioimpedance, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 4: Change in cardiovascular haemodynamics after combined infusion of relaxin and apelin (Innocor)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Cardiac output measured by Innocor, in L/min
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 4: Change in glucose homeostasis after combined infusion of relaxin and apelin (Glucose)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Glucose, in mmol/L
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Substudy 4: Change in glucose homeostasis after combined infusion of relaxin and apelin (C-peptide)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
C-peptide, in pmol/L
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 4: Change in glucose homeostasis after combined infusion of relaxin and apelin (Glucagon)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Glucagon, in pg/ml
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 4: Change in glucose homeostasis after combined infusion of relaxin and apelin (Insulin)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
Insulin, in pmol/L
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Sub-study 4: Change in glucose homeostasis after combined infusion of relaxin and apelin (TNF alpha)
Time Frame: Visit 2 to visit 4, over a period of up to 8 weeks
|
TNF alpha, glucose homeostasis
|
Visit 2 to visit 4, over a period of up to 8 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Joseph Cheriyan, MBCHB, FRCP, Cambridge University Hospitals NHS Foundation Trust
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Cardiovascular Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Vasodilator Agents
- Enzyme Inhibitors
- Membrane Transport Modulators
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Verapamil
- omega-N-Methylarginine
Other Study ID Numbers
- DEFINE (A094666)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Hospital Mutua de TerrassaCompleted
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Oregon Health and Science UniversityCompletedCardiovascular Disease | Cardiovascular Risk FactorsUnited States
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Women's College HospitalUniversity Health Network, Toronto; Sunnybrook Health Sciences Centre; Brigham... and other collaboratorsUnknownCARDIOVASCULAR DISEASESCanada, United States
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Groupe Hospitalier Paris Saint JosephTerminatedCARDIOVASCULAR DISEASESFrance
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University of FloridaUniversity of Alabama at Birmingham; Brown UniversityCompletedCardiovascular Disease | Psychosocial Influence on Cardiovascular DiseaseUnited States
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VA Office of Research and DevelopmentNot yet recruitingCardiovascular DiseaseUnited States
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Baptist Health South FloridaUniversity of California, Los Angeles; Quest Diagnostics-Nichols InsituteActive, not recruitingCardiovascular DiseaseUnited States
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Laval UniversityActive, not recruitingCardiovascular DiseaseCanada
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Penn State UniversityCalifornia Healthcare InstituteCompleted
Clinical Trials on Apelin
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Ain Shams UniversityCompletedRecurrent Pregnancy LossEgypt
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University of EdinburghNHS LothianCompleted
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University Hospital, Basel, SwitzerlandRecruitingEffects of Intravenous [Pyr1]Apelin-13 on Healthy Volunteers With Artificially Induced SIAD (ESCAPE)Hyponatremia | SIAD - Syndrome of Inappropriate AntidiuresisSwitzerland
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University Hospital, ToulouseSociété Francophone du DiabèteCompleted
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Golden Jubilee National HospitalNHS Lothian; Imperial College Healthcare NHS TrustUnknownHeart Failure | Pulmonary Arterial HypertensionUnited Kingdom
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University of CambridgeCompletedCardiovascular DiseaseUnited Kingdom
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Cairo UniversityCompletedDiabetic NephropathiesEgypt
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Imperial College LondonCompletedIdiopathic Pulmonary Arterial HypertensionUnited Kingdom
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University Hospital, ToulouseCompleted
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University of EdinburghUnknown