- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01505673
Adding Liraglutide to High Dose Insulin: Breaking the Cycle
The purpose of this study is to evaluate whether the addition of liraglutide 1.8 mg/day to a high-dose insulin regimen (>1.8 units/kg/day) in patients with uncontrolled (HbA1c >7.5%) type 2 diabetes mellitus will improve blood sugar control.
It also evaluates the effect of liraglutide on liver and pancreatic fat content, explores the mechanism of blood sugar improvement by assessing weight and pancreatic hormone release, and assesses blood pressure, lipid profile, and liver function. Finally it will look at patient quality of life and safety.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Type 2 diabetes is a progressive disease with incessant beta-cell dysfunction that often ultimately requires insulin treatment. Patients requiring high insulin dosages represent a particular treatment challenge and often have uncontrolled glycemia despite progressive dose increases and are especially prone to insulin related lipotoxicity and weight gain.
Glucagon-like peptide agonists (GLP-1) such as liraglutide have many actions that position them to break the vicious cycle in this population through the following mechanisms: (1) weight loss; (2) improved hepatic steatosis; (3) improved pancreatic steatosis; (4) decreased glucagon levels; (5) improved beta-cell function.
The purpose of the study is to demonstrate that liraglutide is both effective and safe when added to a high dose insulin treatment regimen. Liraglutide will improve glycemic control, weight, metabolic parameters, as well as patient satisfaction, with minimal adverse events. The study also proposes to study the mechanisms through which such improvements might occur, especially beta-cell function, glucagon levels, and hepatic and pancreatic fat content.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 4
Kontakter og lokationer
Studiesteder
-
-
Texas
-
Dallas, Texas, Forenede Stater, 75390
- UT Southwestern
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Type 2 diabetes mellitus
- Insulin dose of >1.8 units/kg/day (represents total daily insulin dose, regardless of formulation, regimen, number of daily shots)
- HbA1c ≥ 7.5% and ≤ 11%
- Age ≥ 18
- Stable comorbidities on stable treatment regimens
- Stable dose of all oral hypoglycemics for ≥ 3 months prior to enrollment
- Ability to provide informed consent before any trial-related activities
Exclusion Criteria:
- Type 1 diabetes mellitus
- Any contraindication to the MRI procedure (metallic implants, severe claustrophobia, pregnancy, unable to lie still on a hard table for the duration of the procedure, weight above 400 lb - limit of the MRI table, magnet's inner circumference smaller than the largest body circumference)
- History of any pancreatic disease as it might interfere with the pancreatic TG measurement (i.e. pancreatitis, tumors, cysts, type 1 diabetes, any pancreatic surgery)
- End Stage Renal Disease on dialysis due to increased risk of hypoglycemia, and possible interference with accurate measurement of HbA1c
- Incretin therapy (any GLP-1 agonist or DPP-IV inhibitor)
- Unstable or decompensated comorbidities
- Personal or family history of medullary thyroid carcinoma or MEN-2 syndrome
- Severe gastroparesis
- Pregnancy, breast feeding, intention to become pregnant, or not using adequate contraceptive measures
- Organ transplant recipient or waiting list candidate
- Steroid use (current or potential use during the trial)
- Known/suspected allergy to trial medication, excipients, or related products
- Contraindications to study medications, worded specifically as stated in the product's prescribing information
- Non-English speaking volunteers since no interpreters are available and the safety of the volunteers could be jeopardized if adequate and reliable communication is not possible.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Tredobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Aktiv komparator: Liraglutid
|
Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months
Andre navne:
|
Placebo komparator: Saltvandsinjektion
|
Placebo injection of 1.8mg saline once daily for 6-months
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Glycemic Control Measured by HbA1c
Tidsramme: 6-months
|
HbA1c (%)
|
6-months
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Pancreatic and Hepatic Triglyceride Content
Tidsramme: 6-months
|
Liver Triglyceride and Pancreatic Triglyceride
|
6-months
|
Weight
Tidsramme: 6-months
|
6-months
|
|
Beta-Cell Function
Tidsramme: 6-months
|
Fasting Glucose as a Measure of Beta-Cell Function
|
6-months
|
Glucagon
Tidsramme: 6-months
|
Measured during mixed meal challenge test.
|
6-months
|
Total Daily Insulin Dose
Tidsramme: 6-months
|
The 3 days average of the total daily dose of insulin used within 3 consecutive days prior office visit 6 month.
|
6-months
|
Number of Daily Injections
Tidsramme: 6-months
|
The 3 days average of the number of daily injections performed within 3 consecutive days prior office visit 6 month.
|
6-months
|
Blood Pressure
Tidsramme: 6-months
|
6-months
|
|
Lipid Profile
Tidsramme: 6-months
|
6-months
|
|
Liver Function Blood Test
Tidsramme: 6-months
|
6-months
|
|
Hypoglycemic Events
Tidsramme: 6-months
|
Reported as hypoglycemic events per month by patient as any blood glucose <70 mg/dl or symptoms of hypoglycemia with blood glucose >70 mg/dl
|
6-months
|
Quality of Life Survey (QoL) - General Health Perception
Tidsramme: 6-months
|
General health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 = excellent; 2 = very good; 3 = good; 4 = fair; 5 = poor.
|
6-months
|
Beta-Cell Function
Tidsramme: 6 months
|
Fasting C-peptide as a Measure of Beta-Cell Function
|
6 months
|
Matsuda Index as a Measure of Beta Cell Function
Tidsramme: 6 months
|
The Matsuda index is a measure of insulin sensitivity and has no minimum/maximum values.
Index values are calculated as 500,000/square root of ((fasting glucose x fasting c-peptide x 333) x (mean 120 min post-meal glucose x mean 120 min post-meal c-peptide x 333)).
Higher/lower values = better/worse insulin sensitivity.
|
6 months
|
Beta-cell Function
Tidsramme: 6 Months
|
AUC c-peptide
|
6 Months
|
Ratio (AUC C-peptide/AUC Glucose)
Tidsramme: 6 months
|
6 months
|
|
AUC Glucose
Tidsramme: 6 months
|
6 months
|
|
Quality of Life Survey (QoL) - Current Health Perception
Tidsramme: 6 months
|
Current health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 = much better than 3 months ago; 2 - Somewhat better now than 3 months ago; 3 - About the same; 4 - Somewhat worse now than 3 months ago; 5 Much worse now than 3 months ago.
|
6 months
|
Quality of Life Survey (QoL) - Treatment Satisfaction
Tidsramme: 6 months
|
Quality of Life Survey (QoL) - treatment satisfactionTreatment satisfaction was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.
|
6 months
|
Quality of Life Survey (QoL) - Treatment Impact
Tidsramme: 6 months
|
Treatment impact was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.
|
6 months
|
Quality of Life Survey (QoL) - Social or Vocational Worry
Tidsramme: 6 months
|
Social or vocational worry was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 0-5, where 0 - does not apply; 1 - never; 2 - seldom; 3 - sometimes; 4 - often; 5 - all of the time.
|
6 months
|
Quality of Life Survey (QoL) - Hypoglycemia Fear
Tidsramme: 6 months
|
Hypoglycemia fear was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 - never worry; 2 - rarely water; 3 - sometimes worry; 4 - often worry; 5 - very often worry.
|
6 months
|
Quality of Life Survey (QoL) - Glycemia Control Perception
Tidsramme: 6 months
|
Glycemia control perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a scale score of 1-7, where 1 - extremely controlled and 7 - not at all controlled.
|
6 months
|
Quality of Life Survey (QoL) - Lifestyle Flexibility
Tidsramme: 6 months
|
Lifestyle flexibility was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1 to 5, where 1 - a great deal of choice; 2 - a lot of choice; 3 - some choice; 4 - a little choice; 5 - no choice.
|
6 months
|
Quality of Life Survey (QoL) - Social Stigma
Tidsramme: 6 months
|
Social stigma was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1 to 5, where 1 strongly agree; 2 - somewhat agree; 3 - neither agree nor disagree; 4 - somewhat disagree; 5 - strongly disagree.
|
6 months
|
Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment
Tidsramme: 6 months
|
Satisfaction with insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a scale score of 1 to 7, where 1 extremely satisfied to 7 - not at all satisfied.
|
6 months
|
Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment
Tidsramme: 6 months
|
Willingness to continue insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a scale score of 1 to 7, where 1 extremely willing to 7 - not at all willing.
|
6 months
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Ildiko Lingvay, MD, UT Southwestern
Publikationer og nyttige links
Generelle publikationer
- Vanderheiden A, Harrison L, Warshauer J, Li X, Adams-Huet B, Lingvay I. Effect of Adding Liraglutide vs Placebo to a High-Dose lnsulin Regimen in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA Intern Med. 2016 Jul 1;176(7):939-47. doi: 10.1001/jamainternmed.2016.1540.
- Vanderheiden A, Harrison LB, Warshauer JT, Adams-Huet B, Li X, Yuan Q, Hulsey K, Dimitrov I, Yokoo T, Jaster AW, Pinho DF, Pedrosa I, Lenkinski RE, Pop LM, Lingvay I. Mechanisms of Action of Liraglutide in Patients With Type 2 Diabetes Treated With High-Dose Insulin. J Clin Endocrinol Metab. 2016 Apr;101(4):1798-806. doi: 10.1210/jc.2015-3906. Epub 2016 Feb 24.
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- IIS-000235
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