Diabetes Mellitus, Type 2TrainAiDNCT04945551
Cellular Adaptations to Training in Patients With Type 2 Diabetes
A study testing Aerobic exercise training in people with Diabetes Mellitus, Type 2, run by University of Copenhagen at 1 site in Denmark.
Trial summary
Physical training can improve metabolic health in patients with insulin resistance and/or type 2 diabetes (T2D). The cellular and molecular changes underlying the improvements in metabolic health are multi-factorial and only partly understood, but most likely involve adaptation at a multi-organ level that includes… Read more about this study
- Who is it for?
- Ages 40 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Aerobic exercise training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- 20 Feb 2021to Oct 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Overweight to obese (BMI 28-35 kg/m2)
- Normal resting ECG
- Specific for patients with T2D:
- In antiglycemic treatment with diet +/- metformin, SLGT-2 inhibitors, sulfonylurea, GLP1-RA, or DPPV-4 inhibitors
- Time since diagnosis max 4 yrs
Who cannot join
- Diagnosed with cardiovascular disease (minor to moderate hypertension allowed, defined as prescribed maximally two different antihypertensive drugs)
- Epilepsy
- Kidney disease (GFR<50 ml/min)
- Regular exercise activity
- Inability to perform bicycling and rowing ergometer exercise
- Inability to understand Danish language (written and spoken)
- Specific for patients with T2D:
- Insulin treatment
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Xlab, Faculty of Health and Medical Sciences, University of Copenhagen
Copenhagen, 2200
Flemming Dela, MD, DMSc
About this study
Physical training can improve metabolic health in patients with insulin resistance and/or type 2 diabetes (T2D). The cellular and molecular changes underlying the improvements in metabolic health are multi-factorial and only partly understood, but most likely involve adaptation at a multi-organ level that includes improvements in skeletal muscle glucose uptake and adipose tissue insulin sensitivity.
The aim of this project is to study the transcriptional differences in skeletal muscle and adipose tissue at baseline and after a 3-month physical training program in obese patients with and without T2D and to use this information to identify novel therapeutic targets for improvement of glucose disposal and insulin sensitivity in patients with T2D.
Thus, the investigators aim to find answers to the question: What is the mechanism behind the effect of physical activity on insulin sensitivity in type 2 diabetes?
Read the detailed description
Background and aim
Physical training can improve metabolic health in patients with insulin resistance and/or type 2 diabetes (T2D). The cellular and molecular changes underlying the improvements in metabolic health are multi-factorial and only partly understood, but most likely involve adaptation at a multi-organ level that includes improvements in skeletal muscle glucose uptake and adipose tissue insulin sensitivity.
The literature on the effects of an acute bout of exercise on glucose uptake in skeletal muscle is large, but so far, there is a lack of studies investigating the specific molecular basis for the insulin sensitizing effect of regular physical training.
The aim of this project is to study the transcriptional differences in skeletal muscle and adipose tissue at baseline and after a 3-month physical training program in obese patients with and without T2D and to use this information to identify novel therapeutic targets for improvement of glucose disposal and insulin sensitivity in patients with T2D.
Thus, the investigators aim to find answers to the question: What is the mechanism behind the effect of physical activity on insulin sensitivity in type 2 diabetes?
Methods
Thirty obese patients with (n=15) and without (n=15) type 2 diabetes will be included in the study.
Design: Cohort Study Intervention: 12 weeks intervention period consisting of aerobic exercise training 3 sessions/week, 45 min/session. All training sessions are supervised. Aerobic training is conducted as ergometer bicycle training at an intensity of 70% of maximal oxygen uptake (x2/wk.) and rowing ergometer exercise at 70% of maximal heart rate (x1/wk.). In week 3, 6 and 9 VO2max is measured to ensure sufficient adjustment of the workload during the training sessions.
Experimental methods: Before (1-2 weeks) and after the intervention, the following tests and measurements are performed:
Day A: (Overnight fasting. Duration approx. 3 h)
- Dual energy x-ray absorptiometry (DXA) scan (body composition and body fat)
- Graded exercise test on an ergometer bike (maximal fat oxidation rate)
- Maximal oxygen consumption test (VO2max)
- Handgrip strength (by dynamometer)
- Leg power (Power Rig and sit-to-stand test)
Day B: (Overnight fasting. Duration approx. 9 h)
- 2-step euglycemic, hyperinsulinemic clamp
- Muscle biopsy vastus lateralis
- Fat biopsy subcutaneous lower abdomen
- Flow measurements (Femoral artery by Doppler ultrasound and forearm by strain-gauge plethysmography)
- Energy expenditure (ventilated hood method)
Day A and B are repeated after the training intervention has finished.
Analytical methods:
- Muscle and fat biopsies: Mitochondrial respiratory capacity and reactive oxygen species production. Single nuclei RNA sequencing (snSeq). Fiber type determination and capillarization.
- Blood samples: Hormones, metabolites and substrates (e.g. insulin, catecholamines, cortisol, glucose, lactate, pyruvate, ketone bodies, cytokines, and myokines). Plasma proteomic/peptidomic analysis.
In summary, this study will reveal cell types and genes in skeletal muscle and adipose tissue that are affected by training and/or that shows differential regulation in patients with T2D versus control subjects.
Statistical considerations:
A power calculation indicates that a significant difference in training induced insulin sensitivity will be detectable when n ≥ 10, based on power = 0.95 and level of significance set to P<0.05. This allows for a dropout rate of a 15-20% with some margin. Mixed model analysis will be used for data analysis of phenotypical data, and bioinformatical tools for the snSeq data and for the interaction between gene- and phenotype expression.
Ethical considerations:
The project was approved by The Regional Ethical Committee of the Capital Region (H-20046605) the 15th of December 2020.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Aerobic exercise training
- Keywords
- Diabetes Mellitus, Type 2, Aerobic exercise, Insulin sensitivity
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aerobic exercise trainingBehavioural
12 weeks intervention period consisting of aerobic exercise training 3 sessions/week, 45 min/session. All training sessions are supervised. Aerobic training is conducted as ergometer bicycle training at an intensity of 70% of maximal oxygen uptake (x2/wk.) and rowing ergometer exercise at 70% of maximal heart rate (x1/wk.). In week 3, 6 and 9 VO2 max is measured to ensure sufficient adjustment of the workload during the training sessions.
| Study group | Role | What they receive |
|---|---|---|
| Diabetes | Experimental | Aerobic exercise training Receives: Behavioral: Aerobic exercise training |
| Healthy | Experimental | Aerobic exercise training Receives: Behavioral: Aerobic exercise training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity
Euglycemic hyperinsulinemic clamp
Measured: Change from baseline at 12 weeks
Blood flow
Pulsed-wave Doppler ultrasound (A. femoralis) and venous occlusion strain-gauge plethysmography (forearm)
Measured: Change from baseline at 12 weeks
Gene expression will be quantitatively determined at cellular resolution using single nuclei sequencing
The snSeq data will be analysed using state of the art computational approaches to detect changes in cell type composition and differences in gene expression patterns of specific cell types. These approaches will include: I) normalizations of raw counts; II) feature selection based on most variable genes; III) Conos or Canonical correlation analysis to align the cells across samples; IV) Visualization using dimensionality reduction approaches such as Uniform Approximation and Projection (UMAP) and t-distributed Stochastic Neighbour Embedding (t-SNE); V) RNA velocity and trajectory inference methods to follow changes in cell type identities.
Measured: Change from baseline at 12 weeks
Secondary outcomes (2)
Glucose homeostasis
Changes in HbA1c concentration
Measured: Change from baseline at 12 weeks
Cardiorespiratory fitness
Changes in maximal oxygen uptake
Measured: Baseline and after 3, 6, 9 and 12 weeks of aerobic exercise training
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2021
- Study start20 Feb 2021
- Primary completionJul 2022 (estimated)
- Study completionOct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by University of CopenhagenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Thirty obese patients with (n=15) and without (n=15) type 2 diabetes will be included in the study. Both groups will undergo a 12-week aerobic exercise training intervention.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Principal investigator, Flemming Dela, University of Copenhagen
- Investigators
- Flemming Dela, MD, DMSc, Principal investigator, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04945551
- Sponsor's protocol ID
- Training Adaptations in T2D
- Acronym
- TrainAiD
- Status last verified
- Jun 2021
- First submitted
- 7 Jun 2021
- Last updated
- 30 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Can be provided upon reasonable request
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cellular Adaptations to Training in Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT04945551
- Acronym / sponsor ID
- TrainAiD / Training Adaptations in T2D
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- Diabetes Mellitus, Type 2, Aerobic exercise, Insulin sensitivity
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Collaborators
- Novo Nordisk A/S
- Study start
- 20 Feb 2021 (actual)
- Primary completion
- Jul 2022 (estimated)
- Study completion
- Oct 2023 (estimated)
- First posted
- 30 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Physical training can improve metabolic health in patients with insulin resistance and/or type 2 diabetes (T2D). The cellular and molecular changes underlying the improvements in metabolic health are multi-factorial and only partly understood, but most likely involve adaptation at a multi-organ level that includes improvements in skeletal muscle glucose uptake and adipose tissue insulin sensitivity.
The aim of this project is to study the transcriptional differences in skeletal muscle and adipose tissue at baseline and after a 3-month physical training program in obese patients with and without T2D and to use this information to identify novel therapeutic targets for improvement of glucose disposal and insulin sensitivity in patients with T2D.
Thus, the investigators aim to find answers to the question: What is the mechanism behind the effect of physical activity on insulin sensitivity in type 2 diabetes?
Detailed description
Background and aim
Physical training can improve metabolic health in patients with insulin resistance and/or type 2 diabetes (T2D). The cellular and molecular changes underlying the improvements in metabolic health are multi-factorial and only partly understood, but most likely involve adaptation at a multi-organ level that includes improvements in skeletal muscle glucose uptake and adipose tissue insulin sensitivity.
The literature on the effects of an acute bout of exercise on glucose uptake in skeletal muscle is large, but so far, there is a lack of studies investigating the specific molecular basis for the insulin sensitizing effect of regular physical training.
The aim of this project is to study the transcriptional differences in skeletal muscle and adipose tissue at baseline and after a 3-month physical training program in obese patients with and without T2D and to use this information to identify novel therapeutic targets for improvement of glucose disposal and insulin sensitivity in patients with T2D.
Thus, the investigators aim to find answers to the question: What is the mechanism behind the effect of physical activity on insulin sensitivity in type 2 diabetes?
Methods
Thirty obese patients with (n=15) and without (n=15) type 2 diabetes will be included in the study.
Design: Cohort Study Intervention: 12 weeks intervention period consisting of aerobic exercise training 3 sessions/week, 45 min/session. All training sessions are supervised. Aerobic training is conducted as ergometer bicycle training at an intensity of 70% of maximal oxygen uptake (x2/wk.) and rowing ergometer exercise at 70% of maximal heart rate (x1/wk.). In week 3, 6 and 9 VO2max is measured to ensure sufficient adjustment of the workload during the training sessions.
Experimental methods: Before (1-2 weeks) and after the intervention, the following tests and measurements are performed:
Day A: (Overnight fasting. Duration approx. 3 h)
- Dual energy x-ray absorptiometry (DXA) scan (body composition and body fat)
- Graded exercise test on an ergometer bike (maximal fat oxidation rate)
- Maximal oxygen consumption test (VO2max)
- Handgrip strength (by dynamometer)
- Leg power (Power Rig and sit-to-stand test)
Day B: (Overnight fasting. Duration approx. 9 h)
- 2-step euglycemic, hyperinsulinemic clamp
- Muscle biopsy vastus lateralis
- Fat biopsy subcutaneous lower abdomen
- Flow measurements (Femoral artery by Doppler ultrasound and forearm by strain-gauge plethysmography)
- Energy expenditure (ventilated hood method)
Day A and B are repeated after the training intervention has finished.
Analytical methods:
- Muscle and fat biopsies: Mitochondrial respiratory capacity and reactive oxygen species production. Single nuclei RNA sequencing (snSeq). Fiber type determination and capillarization.
- Blood samples: Hormones, metabolites and substrates (e.g. insulin, catecholamines, cortisol, glucose, lactate, pyruvate, ketone bodies, cytokines, and myokines). Plasma proteomic/peptidomic analysis.
In summary, this study will reveal cell types and genes in skeletal muscle and adipose tissue that are affected by training and/or that shows differential regulation in patients with T2D versus control subjects.
Statistical considerations:
A power calculation indicates that a significant difference in training induced insulin sensitivity will be detectable when n ≥ 10, based on power = 0.95 and level of significance set to P<0.05. This allows for a dropout rate of a 15-20% with some margin. Mixed model analysis will be used for data analysis of phenotypical data, and bioinformatical tools for the snSeq data and for the interaction between gene- and phenotype expression.
Ethical considerations:
The project was approved by The Regional Ethical Committee of the Capital Region (H-20046605) the 15th of December 2020.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Thirty obese patients with (n=15) and without (n=15) type 2 diabetes will be included in the study. Both groups will undergo a 12-week aerobic exercise training intervention.
| Arm | Type | Receives |
|---|---|---|
| Diabetes | Experimental | Behavioral: Aerobic exercise trainingAerobic exercise training |
| Healthy | Experimental | Behavioral: Aerobic exercise trainingAerobic exercise training |
Who may qualify
- Ages
- 40 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Overweight to obese (BMI 28-35 kg/m2)
- Normal resting ECG
- In antiglycemic treatment with diet +/- metformin, SLGT-2 inhibitors, sulfonylurea, GLP1-RA, or DPPV-4 inhibitors
- Time since diagnosis max 4 yrs
Key exclusion criteria (8 listed)
- Diagnosed with cardiovascular disease (minor to moderate hypertension allowed, defined as prescribed maximally two different antihypertensive drugs)
- Epilepsy
- Kidney disease (GFR<50 ml/min)
- Regular exercise activity
- Inability to perform bicycling and rowing ergometer exercise
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aerobic exercise training12 weeks intervention period consisting of aerobic exercise training 3 sessions/week, 45 min/session. All training sessions are supervised. Aerobic training is conducted as ergometer bicycle training at an intensity of 70% of maximal oxygen uptake (x2/wk.) and rowing ergometer exercise at 70% of maximal heart rate (x1/wk.). In week 3, 6 and 9 VO2 max is measured to ensure sufficient adjustment of the workload during the training sessions. | Behavioural | Diabetes, Healthy |
Primary outcome
Insulin sensitivity
Time frame: Change from baseline at 12 weeks
Euglycemic hyperinsulinemic clamp
Blood flow
Time frame: Change from baseline at 12 weeks
Pulsed-wave Doppler ultrasound (A. femoralis) and venous occlusion strain-gauge plethysmography (forearm)
Gene expression will be quantitatively determined at cellular resolution using single nuclei sequencing
Time frame: Change from baseline at 12 weeks
The snSeq data will be analysed using state of the art computational approaches to detect changes in cell type composition and differences in gene expression patterns of specific cell types. These approaches will include: I) normalizations of raw counts; II) feature selection based on most variable genes; III) Conos or Canonical correlation analysis to align the cells across samples; IV) Visualization using dimensionality reduction approaches such as Uniform Approximation and Projection (UMAP) and t-distributed Stochastic Neighbour Embedding (t-SNE); V) RNA velocity and trajectory inference methods to follow changes in cell type identities.
2 secondary outcomes
Glucose homeostasis
Time frame: Change from baseline at 12 weeks
Cardiorespiratory fitness
Time frame: Baseline and after 3, 6, 9 and 12 weeks of aerobic exercise training
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2021.
- Individual participant dataSharing planned: No. Can be provided upon reasonable request
Related trials for Diabetes Mellitus, Type 2
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Flemming Dela, MD, DMSc principal investigator
University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aerobic exercise training in people with Diabetes Mellitus, Type 2, run by University of Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Maria Hansen, MD (+4529210442, mariahan@sund.ku.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin sensitivity (time frame: Change from baseline at 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2021.