- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03769883
The Effects of Different Doses of Exercise on Pancreatic β-cell Function in Patients With Newly Diagnosed Type 2 Diabetes (DOSE-EX)
The Effects of Different Doses of Exercise on Pancreatic ß-cell Function in Patients With Newly Diagnosed Type 2 Diabetes (DOSE-EX): A Randomized Clinical Trial
This project will provide an exercise-based lifestyle intervention with the potential to reduce complications for patients with short standing type 2 diabetes (T2D). While exercise is widely accepted as a component of T2D management, little is known about the additive effect of exercise when combined with a diet on T2D pathophysiology and mechanisms believed to lead to micro- and macrovascular complications. Moreover, the necessary dose of exercise to revert the progression of T2D and the related complications has not been investigated. A large-scale randomized controlled trial (RCT) will be essential to document the effectiveness on reducing the risk of T2D complications. However, prior to conducting a large-scale RCT, we need to specify the exercise dose that efficiently compliments the diet.
In a 4-armed randomized, clinical trial (N=80 T2D patients, T2D duration < than 7 years) we aim to investigate 1) the potential additive role of exercise on pancreatic β-cell function in patients with T2D when combined with a diet, 2) the causal relationship between lifestyle-induced reductions in glycaemic variability, oxidative stress and low-grade inflammation and, 3) the role of exercise in rescuing dysregulated muscle progenitor cells. The participants will be randomly allocated to either a) control, b) diet, c) diet and exercise 3 times/week or d) diet and exercise 6 times/week for 16 weeks. Prior to, during and following the interventions, all participants will undergo extensive testing.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
A 4-armed, 16-week, parallel-group, assessor-blinded, randomized, clinical trial. Participants will be randomly allocated (1:1:1:1), stratified by sex
Interventions:
The lifestyle interventions will consist of two main components; 1) increased physical activity and structured exercise and/or 2) a dietary intervention aiming at a weight loss. Whereas there will be no differences in the dietary intervention between the lifestyle groups, the volume of physical activity and structured exercise will vary according to the frequencies of the structured exercise sessions.
The study groups are prescribed:
- Control group (CON): No intervention
- Dietary control (DCON): Dietary intervention (see below)
- Moderate Exercise Dose (MED): Two aerobic training sessions per week of 45-60 min duration and one session per week with combined aerobic (30-35 min) and resistance (30 min) training and a dietary intervention (described below)
- High Exercise Dose (HED): Four aerobic training sessions per week of 45-60 min duration and two sessions per week with combined aerobic (30-35 min) and resistance (30 min) training and a dietary intervention (described below)
Detailed description of the intervention components. Exercise: The training protocol will be adapted based on a previous study where the T2D participants were prescribed 6 weekly sessions of aerobic training alone or combined aerobic and resistance training (averaging 360-420 min of exercise per week). As previous analyses suggest that there may be an inverse dose-response relationship between reductions in HbA1c and aerobic exercise volume, this parameter will be used to adapt the training protocol. As the effect of exercise on HbA1c is closer related to the number of training sessions rather than intensity15, we will reduce the number of sessions by 50%, to three sessions/week in the moderate exercise dose group and maintain the original session frequency in the high dose exercise group (six sessions/week).Training will be supervised and monitored to ensure intensity and compliance.
Dietary intervention and intended weight loss (DCON, MED and HED: The dietary intervention will be based on the recommendations from the American Diabetes Association (ADA) with increased focus on macronutrient quality. The macronutrient distributions are in line with the current guidelines from the national Diabetes Association and Canadian guidelines, where individualization in macronutrient distribution should lie within the range of 45-60 energy% carbohydrate, 15-20 energy% protein and 20-35 energy% fat. Thus, the dietary intervention emphasis will be on low glycemic index and low glycemic load in shape of non-processed foods and will aim at reducing saturated fat intake <7 energy%.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Inge Holm
- Phone Number: +45 35 45 76 41
- Email: inge.holm@regionh.dk
Study Contact Backup
- Name: Bente K Pedersen, Dr Med
- Phone Number: +45 35 45 76 41
- Email: inge.holm@regionh.dk
Study Locations
-
-
-
Copenhagen, Denmark, 2100
- Recruiting
- Center for Physical Activity Research, Copenhagen University Hospital
-
Contact:
- Mathias Ried-Larsen, PhD
- Phone Number: 0045 35 45 06 99
- Email: mathias.ried-larsen@regionh.dk
-
Contact:
- Inge Holm
- Phone Number: 0045 35 45 76 21
- Email: inge.holm@regionh.dk
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Diagnosed with diabetes type 2 and/or HbA1c ≥ 48 mmol/mol if no treatment with anti-diabetic medication and/or use of antidiabetic medication
Caucasian
No diagnose of Type 1 diabetes, mature onset diabetes of the young, Latent autoimmune diabetes of adults
T2D 0-6 years of duration
No treatment with insulin
Body Mass Index (BMI) >27 kg/m2 and <40 kg/m2
No known or signs of intermediate or severe microvascular complications to diabetes (retino-, neuro- or nephropathy)
No known cancer
No Known lung disease
No known cardiovascular disease
No known thyroid disease
No known liver disease
No known autoimmune disease
No other endocrine disorder causing obesity
No current treatment with anti-obesity medication
No current treatment with anti-inflammatory medication
No weight loss of > 5kg within the last 6 months
No diagnose of depression or treatment with anti-depressive medication, ongoing or within the last three months before enrolment
No diagnose of psychiatric disorder or treatment with anti-psychotic medication
No history of suicidal behavior or ideations within the last three months before enrolment
No previous surgical treatment for obesity (excluding liposuction > 1 year prior to enrolment)
Not pregnant/considering pregnancy
No functional impairments that prevents the performance of intensive exercise
Accept of medical regulation by the U-TURN endocrinologist
Inactivity, defined as < 1,5 hours of structured physical activity pr. week at moderate intensity and cycling < 30 minutes/5 km pr. day at moderate intensity (moderate intensity = out of breath but able to speak)
No participation in other research intervention studies
Exclusion Criteria:
HbA1c: >=75 mmol/mol with no glucose lowering medications
HbA1c: >=64 mmol/mol with mono glucose lowering therapy (if compliant with the prescription)
HbA1c: >=57 mmol/mol with >=dual glucose lowering therapy (if compliant with the prescription)
estimated glomerular filtration rate<60 mL/min
Protein or glucose in the urine at pre-screening
No biochemical sign of other major diseases
Presence of circulating glutamate-decarboxylase anti body (GAD) 65
Objective findings that contraindicates participation in intensive exercise
Anamnestic findings that contraindicates participation in the study
Unable to allocate the needed time to fulfill the intervention
Language barrier, mental incapacity, unwillingness or inability to understand and be able to complete the interventions
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: Control
No intervention
|
|
Experimental: Dietary control (DCON)
The macro-nutrient distributions are in line with the current guidelines from the national Diabetes Association and Canadian guidelines, where individualization in macronutrient distribution should lie within the range of 45-60E% carbohydrate, 15-20E% protein and 20-35E% fat.
The dietary plan will aim at reducing saturated fat intake <7E% aiming at a caloric deficit of 500 kilo calories/day
|
Dietary intervention
|
Experimental: Moderate Exercise Dose (MED)
Two aerobic training sessions per week of 45-60 min duration and one session per week with combined aerobic (30-35 min) and resistance (30 min) training and a dietary intervention (as above)
|
The participants will undergo diet or combined diet and exercise.
The exercise will be provided at different volumes
|
Experimental: High Exercise Dose (HED)
Four aerobic training sessions per week of 45-60 min duration and two sessions per week with combined aerobic (30-35 min) and resistance (30 min) training and a dietary intervention (as above)
|
The participants will undergo diet or combined diet and exercise.
The exercise will be provided at different volumes
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pancreatic beta-cell function (Per protocol)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
The change in the late-phase disposition index (DI) during the final 30 minutes of hyperglycemic phase of the hyperglycemic clamp.
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pancreatic beta-cell function (Intention to treat)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
As for per protocol
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Glucagon like peptide 1 sensitivity (c-peptide)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Glucagon like peptide 1 stimulated C-peptide secretion
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Glucagon like peptide 1 sensitivity (glucagon)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Glucagon like peptide 1 stimulated glucagon secretion
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Glucagon like peptide 1 sensitivity (insulin)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Glucagon like peptide 1 stimulated insulin secretion
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Arginine sensitivity (insulin)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Arginine stimulated insulin secretion
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Arginine sensitivity (c-peptide)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Arginine stimulated C-peptide secretion
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Arginine sensitivity (glucagon)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Arginine stimulated glucagon secretion
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Early phase disposition index (c-peptide)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in 1st phase C-peptide secretion defined as the peak concentration during the initial 10 minutes of the hyperglycaemic clamp
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Early phase disposition index (insulin)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in 1st phase insulin secretion defined as the peak concentration during the initial 10 minutes of the hyperglycaemic clamp
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Glucose clearance
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Rate of glucose clearance (stable isotope infusion) during steady state hyperglycemia
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Glucose appearance
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Rate of glucose appearance (stable isotope infusion) during steady state hyperglycemia
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Insulin sensitivity
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in mean Glucose infusion rate over last 30 min of clamp phase/(mean insulin×glucose
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Mean amplitude of glycemic excursions
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Mean amplitude of glycemic excursions (MAGE - calculated based on min 3 days sensor glucose profiles)
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Coefficient of glucose variation
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Coefficient of variation defined as (mean glucose/the standard deviation (SD)) of min 3 days sensor glucose profiles
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Mean glucose levels
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in the mean glucose levels (calculated based on min 3 days sensor glucose profiles)
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Time in hyperglycemia
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in time in hyperglycaemia (calculated based on min 3 days sensor glucose profiles)
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Time in hypoglycemia
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in time in hypoglycaemia from min 3 days sensor glucose profiles
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Pancreatic fat
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Pancreatic fat
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Hepatic fat
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Hepatic fat
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Visceral fat
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in visceral fat
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Total fat mass
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Total fat mass
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Total fat free mass
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Total fat free mass
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Total lean body mass
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Total lean body mass
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Android fat mass
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in Android fat mass
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Gynoid fat mass
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in gynoid fat mass
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Body weight
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in body weight
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Body mass index
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in body mass index
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Systemic oxidative stress (RNA)
Time Frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Change in 8-oxo-guanosine
|
From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Systemic oxidative stress (DNA)
Time Frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Change in 8-oxo-deoxoguonase
|
From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Advanced glycation end-products (AGE)
Time Frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Change in AGE
|
From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
The circulating receptor for advanced glycation end-products (sRAGE)
Time Frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Change in sRAGE
|
From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Markers of low-grade inflammation
Time Frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Change in inflammatory markers (e.g.
high sensitive C-reactive protein, interferon-ϒ, interleukin-10, interleukin-8, interleukin-6, interleukin-1, TNFα)
|
From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Glycated haemoglobin type 1AC (HbA1c)
Time Frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Change in HbA1c
|
From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Total cholesterol
Time Frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Change in total cholesterol
|
From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Total triglyceride
Time Frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Change in total triglyceride
|
From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Low density lipoprotein (LDL)
Time Frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Change in LDL
|
From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
High density lipoprotein (HDL)
Time Frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Change in HDL
|
From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
|
Systolic blood pressure
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change systolic blood pressures
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Diastolic blood pressure
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change diastolic blood pressure
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Glucose tolerance
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change incremental and total area under the curve (glucose, c-peptide, insulin) during a mixed meal tolerance test
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Gastric emptying (AUC)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in the AUC (paracetamol) during a mixed meal tolerance test
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Gastric emptying (Rate of appearance)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in rate of appearance of paracetamol during a mixed meal tolerance test
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Physical fitness (VO2max)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in physical fitness (VO2) during a progressive maximal bicycle ergometer test
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Muscular 1 repetition max (strength)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in 1 repetition max
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Total physical activity
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in objectively measured physical activity (counts per minute)
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Moderate and vigorous physical activity (MVPA)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in time spend on MVPA
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Sedentary time (SED)
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in time spend on SED
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Physical well being
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in physical well being (Based on the physical dimension score from short-form 36, range 0-100)
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Mental well being
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in mental well being (Based on the mental dimension score from Short-form 36) (range 0-100)
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Satiety
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in self-reported satiety (VAS) during a mixed meal tolerance test (range 0-10)
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Muscular metabolic function
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in metabolic function (Based on muscle biopsies in a subset of participants, N=16-32))
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Fat tissue metabolic function
Time Frame: From baseline (0 weeks) to follow-up (16 weeks)
|
Change in metabolic function (Based on muscle biopsies in a subset of participants, N=16-32)
|
From baseline (0 weeks) to follow-up (16 weeks)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mathias Ried-Larsen, PhD, Centre for Physical Activity Research, Righospitalet
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- H-18038298
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
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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