Diabetes Mellitus, Type 2RESTORENCT04565418
Exercise to Restore 24h Rhythms in Metabolism
A study testing High-intensity interval training in people with Diabetes Mellitus, Type 2 and Insulin Resistance, run by Maastricht University at 1 site in Netherlands.
Trial summary
This study will investigate the effect of exercise training on 24h rhythms in substrate metabolism in overweight subjects with impaired glucose tolerance. Subjects will perform exercise training for 12 weeks. Read more about this study
- Who is it for?
- Ages 40 to 75 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2, Insulin Resistance
- What is being tested?
- High-intensity interval training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- 26 Jan 2021to 24 Apr 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 75 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Caucasian
- Healthy (as determined by dependent physician)
- Overweight: BMI 25 - 35 kg/m2
- Prediabetic based on one or a combination of the following criteria:
- Impaired Glucose Tolerance (IGT): plasma glucose values ≥ 7.8 mmol/l and ≤ 11.1 mmol/l 120 minutes after glucose drink consumption during OGTT in screening.
- Impaired Fasting Glucose (IFG): Fasting plasma glucose ≥ 6.1 mmol/l and ≤ 6.9 mmol/l.
Show all 10Show fewer
- Insulin Resistance: glucose clearance rate ≤ 360ml/kg/min, as determined using the OGIS120 model.
- HbA1c of 5.7-6.4%.
- Regular sleeping time (normally 7 - 9h daily)
- Stable dietary habits: no weight gain or loss > 3kg in the last three months.
Who cannot join
- Use of anticoagulants
- Previously diagnosed with type 2 diabetes
- Current alcohol consumption > 20 grams alcohol/day
- Extreme early bird or extreme night person (score ≤ 30 or ≥ 70 on MEQ-SA questionnaire)
- Heavily varying sleep-wake rhythm
- Nightshift work during last 3 months
Show all 10Show fewer
- Travel across > 1 time zone in the last 3 months
- Significant food allergies/intolerance (seriously hampering study meals)
- Using > 400mg caffeine daily (more than 4 coffee or energy drink)
- Smoking
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exercise to Restore 24h Rhythmicity in Substrate Metabolism of Prediabetes Subjects
This study will investigate the effect of exercise training on 24h rhythms in substrate metabolism in overweight subjects with impaired glucose tolerance. Subjects will perform exercise training for 12 weeks. Before and after the exercise period, they will be admitted to research facilities for 45 hours to assess 24h rhythms in substrate metabolism. In a single-arm longitudinal design, subjects will serve as their own control.
Read the detailed description
Recent evidence shows that pre-diabetes is characterized by marked alterations in 24h substrate metabolism, indicating metabolic inflexibility with an inability to fully switch to fat oxidation during the night. Whereas exercise has been shown to promote mitochondrial function and insulin sensitivity, it is unknown to if exercise training is able to restore 24h rhythmicity in overall substrate metabolism and muscle metabolism in human subjects with pre-diabetes.
In this single-arm longitudinal design, subjects will serve as their own control. Subjects will perform high-intensity interval training for 12 weeks (3x times per week) on a cycle ergometer at the research facility. Pre and post exercise, subjects will stay in a metabolic chamber and adhere to a relatively normal life-style in order to standardize the main 24h measurement period. As the primary outcome, substrate metabolism will be measured with a ventilated hood system and by indirect calorimetry in the chambers. Muscle biopsies from the vastus lateralis and frequent blood samples will also be taken over the course of the 24h. Thereby, ex-vivo skeletal muscle mitochondrial function and muscle clock gene expression will serve as the main secondary outcomes.
- Conditions
- Diabetes Mellitus, Type 2, Insulin Resistance
- Being tested
- High-intensity interval training
- Keywords
- Circadian rhythm
- 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.
High-intensity interval trainingBehavioural
3 times per week high-intensity interval training (HIIT) will be performed on a cycle ergometer for 12 weeks adding up to 36 HIIT sessions
| Study group | Role | What they receive |
|---|---|---|
| Exercise training | Experimental | 12 week high-intensity interval training (3 sessions per week): Before and after exercise, subjects are kept at the research facility to adhere to a standardized living protocol, mimicking a normal daily living situation. During the study, multiple tests will be performed, including muscle biopsies, blood draws and indirect calorimetry. Receives: Behavioral: High-intensity interval training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in 24 rhythm in whole-body energy metabolism (energy expenditure)
Energy expenditure (kJ/min) measured by indirect calorimetry
Measured: measured at 8:00, 13:00, 18:00, 23:00, 04:00 of the main test day before and after 12 weeks of exerise
Change in 24 rhythm in whole-body energy metabolism (glucose oxidation)
Energy expenditure (kJ/min) measured by indirect calorimetry
Measured: measured at 8:00, 13:00, 18:00, 23:00, 04:00 of the main test day before and after 12 weeks of exercise
Change in 24 rhythm in whole-body energy metabolism (fat oxidation)
Energy expenditure (kJ/min) measured by indirect calorimetry
Measured: measured at 8:00, 13:00, 18:00, 23:00, 04:00 of the main test day before and after 12 weeks of exercise
Secondary outcomes (13)
Change in 24 rhythm in skeletal muscle mitochondrial respiration
O2-flux (pmol/mg/s) measured with high resolution respirometry
Measured: measured at 8:00, 13:00, 23:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in muscle protein levels of markers involved in molecular clock and mitochondrial metabolism
Quantify protein levels by Western blots
Measured: measured at 8:00, 13:00, 23:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in muscle DNA of markers involved in molecular clock and mitochondrial metabolism
Quantify DNA by qPCR
Measured: measured at 8:00, 13:00, 23:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in muscle DNA involved in molecular clock and mitochondrial metabolism.
Quantify DNA by micro-array
Measured: measured at 8:00, 13:00, 23:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in muscle mRNA markers involved in molecular clock and mitochondrial metabolism
Quantify mRNA levels by micro array
Measured: measured at 8:00, 13:00, 23:00 of the main test day before and after 12 weeks of exercise
Change in 24 rhythm of markers of normal 24h rhythm (cortisol)
Blood cortisol levels
Measured: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Change in 24 rhythm of markers of normal 24h rhythm (melatonin)
Blood melatonin levels
Measured: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Change in 24 rhythm of markers of normal 24h rhythm (core body temperature)
Core body temperature measured by an ingested telemetric pill
Measured: measured continuously for 24 hours on the main test day before and after 12 weeks of exercise
Change in 24h rhythm in serum glucose
Serum glucose levels determined from venous blood draws
Measured: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in serum insulin
Serum insulin levels determined from venous blood draws
Measured: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in serum free fatty acids (FFA)
Serum FFA levels determined from venous blood draws
Measured: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in serum triglycerides
Serum triglycerides levels determined from venous blood draws
Measured: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in serum cholesterol
Serum cholesterol levels determined from venous blood draws
Measured: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2020
- Study start26 Jan 2021
- Primary completion22 Dec 2022
- Study completion24 Apr 2023
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.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04565418
- Sponsor's protocol ID
- NL73834.068.20
- Acronym
- RESTORE
- Status last verified
- May 2023
- First submitted
- 17 Aug 2020
- Last updated
- 24 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exercise to Restore 24h Rhythmicity in Substrate Metabolism of Prediabetes Subjects
- ClinicalTrials.gov ID
- NCT04565418
- Acronym / sponsor ID
- RESTORE / NL73834.068.20
- Conditions
- Diabetes Mellitus, Type 2, Insulin Resistance
- Keywords
- Circadian rhythm
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Maastricht UniversityUniversity, hospital or other
- Study start
- 26 Jan 2021 (actual)
- Primary completion
- 22 Dec 2022 (actual)
- Study completion
- 24 Apr 2023 (actual)
- First posted
- 25 Sep 2020 (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.
This study will investigate the effect of exercise training on 24h rhythms in substrate metabolism in overweight subjects with impaired glucose tolerance. Subjects will perform exercise training for 12 weeks. Before and after the exercise period, they will be admitted to research facilities for 45 hours to assess 24h rhythms in substrate metabolism. In a single-arm longitudinal design, subjects will serve as their own control.
Detailed description
Recent evidence shows that pre-diabetes is characterized by marked alterations in 24h substrate metabolism, indicating metabolic inflexibility with an inability to fully switch to fat oxidation during the night. Whereas exercise has been shown to promote mitochondrial function and insulin sensitivity, it is unknown to if exercise training is able to restore 24h rhythmicity in overall substrate metabolism and muscle metabolism in human subjects with pre-diabetes.
In this single-arm longitudinal design, subjects will serve as their own control. Subjects will perform high-intensity interval training for 12 weeks (3x times per week) on a cycle ergometer at the research facility. Pre and post exercise, subjects will stay in a metabolic chamber and adhere to a relatively normal life-style in order to standardize the main 24h measurement period. As the primary outcome, substrate metabolism will be measured with a ventilated hood system and by indirect calorimetry in the chambers. Muscle biopsies from the vastus lateralis and frequent blood samples will also be taken over the course of the 24h. Thereby, ex-vivo skeletal muscle mitochondrial function and muscle clock gene expression will serve as the main secondary outcomes.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Exercise training | Experimental | Behavioral: High-intensity interval training12 week high-intensity interval training (3 sessions per week): Before and after exercise, subjects are kept at the research facility to adhere to a standardized living protocol, mimicking a normal daily living situation. During the study, multiple tests will be performed, including muscle biopsies, blood draws and indirect calorimetry. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Caucasian
- Healthy (as determined by dependent physician)
- Overweight: BMI 25 - 35 kg/m2
- Prediabetic based on one or a combination of the following criteria:
- Regular sleeping time (normally 7 - 9h daily)
Key exclusion criteria (10 listed)
- Use of anticoagulants
- Previously diagnosed with type 2 diabetes
- Current alcohol consumption > 20 grams alcohol/day
- Extreme early bird or extreme night person (score ≤ 30 or ≥ 70 on MEQ-SA questionnaire)
- Heavily varying sleep-wake rhythm
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 |
|---|---|---|
| High-intensity interval training3 times per week high-intensity interval training (HIIT) will be performed on a cycle ergometer for 12 weeks adding up to 36 HIIT sessions | Behavioural | Exercise training |
Primary outcome
Change in 24 rhythm in whole-body energy metabolism (energy expenditure)
Time frame: measured at 8:00, 13:00, 18:00, 23:00, 04:00 of the main test day before and after 12 weeks of exerise
Energy expenditure (kJ/min) measured by indirect calorimetry
Change in 24 rhythm in whole-body energy metabolism (glucose oxidation)
Time frame: measured at 8:00, 13:00, 18:00, 23:00, 04:00 of the main test day before and after 12 weeks of exercise
Energy expenditure (kJ/min) measured by indirect calorimetry
Change in 24 rhythm in whole-body energy metabolism (fat oxidation)
Time frame: measured at 8:00, 13:00, 18:00, 23:00, 04:00 of the main test day before and after 12 weeks of exercise
Energy expenditure (kJ/min) measured by indirect calorimetry
13 secondary outcomes
Change in 24 rhythm in skeletal muscle mitochondrial respiration
Time frame: measured at 8:00, 13:00, 23:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in muscle protein levels of markers involved in molecular clock and mitochondrial metabolism
Time frame: measured at 8:00, 13:00, 23:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in muscle DNA of markers involved in molecular clock and mitochondrial metabolism
Time frame: measured at 8:00, 13:00, 23:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in muscle DNA involved in molecular clock and mitochondrial metabolism.
Time frame: measured at 8:00, 13:00, 23:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in muscle mRNA markers involved in molecular clock and mitochondrial metabolism
Time frame: measured at 8:00, 13:00, 23:00 of the main test day before and after 12 weeks of exercise
Change in 24 rhythm of markers of normal 24h rhythm (cortisol)
Time frame: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Change in 24 rhythm of markers of normal 24h rhythm (melatonin)
Time frame: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Change in 24 rhythm of markers of normal 24h rhythm (core body temperature)
Time frame: measured continuously for 24 hours on the main test day before and after 12 weeks of exercise
Change in 24h rhythm in serum glucose
Time frame: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in serum insulin
Time frame: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in serum free fatty acids (FFA)
Time frame: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in serum triglycerides
Time frame: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Change in 24h rhythm in serum cholesterol
Time frame: every two hours for 24 hours beginning at 08:00 of the main test day before and after 12 weeks of exercise
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2023.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High-intensity interval training in people with Diabetes Mellitus, Type 2 and Insulin Resistance, run by Maastricht University at 1 site in Netherlands.
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 10 inclusion and 10 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: finished, as of the sponsor's last update on 24 May 2023. 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 Netherlands. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in 24 rhythm in whole-body energy metabolism (energy expenditure) (time frame: measured at 8:00, 13:00, 18:00, 23:00, 04:00 of the main test day before and after 12 weeks of exerise). 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 24 May 2023.