Diabetes Mellitus, Type 2NCT03733743
Day-night Rhythm in Muscle Metabolism of Prediabetics
A study testing Standardized living protocol in people with Diabetes Mellitus, Type 2 and Insulin Resistance, run by Maastricht University at 1 site in Netherlands.
Trial summary
This study evaluates the existence of a day-night rhythm in skeletal muscle energy metabolism in prediabetic subjects. Subjects will stay at the research facility for 44 hours with a standardized living protocol during which several measurements of skeletal muscle and whole body energy metabolism will be performed. 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?
- Standardized living protocol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- 9 Jul 2018to 29 Mar 2019
- 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.
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- 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: Day-night Rhythm in Muscle Metabolism of Prediabetic Subjects
This study evaluates the existence of a day-night rhythm in skeletal muscle energy metabolism in prediabetic subjects. Subjects will stay at the research facility for 44 hours with a standardized living protocol during which several measurements of skeletal muscle and whole body energy metabolism will be performed.
Read the detailed description
Recent evidence from both observational and experimental studies indicates that disobedience of a normal day-night rhythm negatively influences metabolic and cardiovascular health, possibly leading to obesity and type 2 diabetes mellitus (T2DM). An important hallmark of obesity and T2DM is a decreased skeletal muscle mitochondrial function. Interestingly, recent research indicates that also skeletal muscle mitochondrial function is under the influence of a day-night rhythm. In this study, the presence of a day-night rhythm in skeletal muscle energy metabolism (in particular mitochondrial function) of overweight prediabetic participants will be investigated. During this study, subjects will stay at the research unit for 44 hours, with standardized meals and sleeping time. Five muscle biopsies (v. lateralis) and frequent blood draws will be taken. In addition, indirect calorimetry measurements will be performed.
- Conditions
- Diabetes Mellitus, Type 2, Insulin Resistance
- Being tested
- Standardized living protocol
- 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.
Standardized living protocolOther
Subjects stay at the research facility for 44 hours and adhere to a standard sleeping, eating and activity protocol. During this protocol, multiple measurements will be performed including skeletal muscle biopsies (m. vastus lateralis), blood draws, indirect calorimetry and MRS measurements.
| Study group | Role | What they receive |
|---|---|---|
| Standardized living protocol | Other | 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, MRS measurements and indirect calorimetry. Receives: Other: Standardized living protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Day-night rhythm in skeletal muscle mitochondrial respiration
O2-flux (pmol/mg/s) measured with high resolution respirometry
Measured: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Secondary outcomes (16)
Day-night rhythm in whole-body energy metabolism (energy expenditure)
Energy expenditure (kJ/min) measured by indirect calorimetry
Measured: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm in whole-body energy metabolism (glucose oxidation)
glucose oxidation (g/min) measured by indirect calorimetry
Measured: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm in whole-body energy metabolism (fat oxidation)
fat oxidation (g/min) measured by indirect calorimetry
Measured: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm in muscle protein levels of markers involved in molecular clock and mitochondrial metabolism.
Quantify protein levels by Western blots
Measured: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm in muscle DNA of markers involved in molecular clock and mitochondrial metabolism.
Quantify DNA by qPCR
Measured: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm in muscle DNA involved in molecular clock and mitochondrial metabolism.
Quantify DNA by micro-array
Measured: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm in muscle mRNA markers involved in molecular clock and mitochondrial metabolism.
Quantify mRNA levels by micro array
Measured: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm of markers of normal day-night rhythm (cortisol)
Blood cortisol levels
Measured: measured on day two, every two hours for 24 hours beginning at 08:00
Day-night rhythm of in markers of normal day-night rhythm (core body temperature)
Core body temperature measured by an ingested telemetric pill.
Measured: measured continuously for 24 hours on day two
Day-night rhythm of in markers of normal day-night rhythm (melatonin)
Blood melatonin levels.
Measured: measured on day two, every two hours for 24 hours beginning at 08:00
Day-night rhythm in serum glucose
Serum glucose levels determined from venous blood draws
Measured: measured on day two, every two hours for 24 hours beginning at 08:00
Day-night rhythm in serum insulin
Serum insulin levels determined from venous blood draws
Measured: measured on day two, every two hours for 24 hours beginning at 08:00
Day-night rhythm in serum free fatty acids (FFA)
Serum FFA levels determined from venous blood draws
Measured: measured on day two, every two hours for 24 hours beginning at 08:00
Day-night rhythm in serum triglycerides
Serum triglyceride levels determined from venous blood draws
Measured: measured on day two, every two hours for 24 hours beginning at 08:00
Day-night rhythm in serum cholesterol
Serum cholesterol levels determined from venous blood draws
Measured: measured on day two, every two hours for 24 hours beginning at 08:00
Change in energy status of the heart between morning and evening
variation in phosphorus metabolites measured by Magnetic Resonance Imaging and - Spectroscopy (MRI/MRS)
Measured: Measured on first study day 5:30 PM (duration 45 minutes), second study day 7:30 AM (duration 45 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2018
- Study start9 Jul 2018
- Primary completion20 Mar 2019
- Study completion29 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- Model description
- Standardized living protocol
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University Medical Center
- Responsible party
- Sponsor
- Investigators
- Patrick Schrauwen, PhD, Principal investigator, Maastricht University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03733743
- Sponsor's protocol ID
- NL64753.068.18
- Status last verified
- Sep 2018
- First submitted
- 19 Sep 2018
- Last updated
- 16 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Harmsen JF, Kotte M, Habets I, Bosschee F, Frenken K, Jorgensen JA, de Kam S, Moonen-Kornips E, Cissen J, Doligkeit D, van de Weijer T, Erazo-Tapia E, Buitinga M, Hoeks J, Schrauwen P. Exercise training modifies skeletal muscle clock gene expression but not 24-hour rhythmicity in substrate metabolism of men with insulin resistance. J Physiol. 2024 Dec;602(23):6417-6433. doi: 10.1113/JP285523. Epub 2023 Dec 5.
PubMed 38051503Wefers J, Connell NJ, Fealy CE, Andriessen C, de Wit V, van Moorsel D, Moonen-Kornips E, Jorgensen JA, Hesselink MKC, Havekes B, Hoeks J, Schrauwen P. Day-night rhythm of skeletal muscle metabolism is disturbed in older, metabolically compromised individuals. Mol Metab. 2020 Nov;41:101050. doi: 10.1016/j.molmet.2020.101050. Epub 2020 Jul 11.
PubMed 32659272
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Day-night Rhythm in Muscle Metabolism of Prediabetic Subjects
- ClinicalTrials.gov ID
- NCT03733743
- Acronym / sponsor ID
- NL64753.068.18
- Conditions
- Diabetes Mellitus, Type 2, Insulin Resistance
- Keywords
- Circadian Rhythm
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Maastricht UniversityUniversity, hospital or other
- Collaborators
- Maastricht University Medical Center
- Study start
- 9 Jul 2018 (actual)
- Primary completion
- 20 Mar 2019 (actual)
- Study completion
- 29 Mar 2019 (actual)
- First posted
- 7 Nov 2018 (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 evaluates the existence of a day-night rhythm in skeletal muscle energy metabolism in prediabetic subjects. Subjects will stay at the research facility for 44 hours with a standardized living protocol during which several measurements of skeletal muscle and whole body energy metabolism will be performed.
Detailed description
Recent evidence from both observational and experimental studies indicates that disobedience of a normal day-night rhythm negatively influences metabolic and cardiovascular health, possibly leading to obesity and type 2 diabetes mellitus (T2DM). An important hallmark of obesity and T2DM is a decreased skeletal muscle mitochondrial function. Interestingly, recent research indicates that also skeletal muscle mitochondrial function is under the influence of a day-night rhythm. In this study, the presence of a day-night rhythm in skeletal muscle energy metabolism (in particular mitochondrial function) of overweight prediabetic participants will be investigated. During this study, subjects will stay at the research unit for 44 hours, with standardized meals and sleeping time. Five muscle biopsies (v. lateralis) and frequent blood draws will be taken. In addition, indirect calorimetry measurements will be performed.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Standardized living protocol
| Arm | Type | Receives |
|---|---|---|
| Standardized living protocol | Other | Other: Standardized living protocolSubjects 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, MRS measurements 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 |
|---|---|---|
| Standardized living protocolSubjects stay at the research facility for 44 hours and adhere to a standard sleeping, eating and activity protocol. During this protocol, multiple measurements will be performed including skeletal muscle biopsies (m. vastus lateralis), blood draws, indirect calorimetry and MRS measurements. | Other | Standardized living protocol |
Primary outcome
Day-night rhythm in skeletal muscle mitochondrial respiration
Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
O2-flux (pmol/mg/s) measured with high resolution respirometry
16 secondary outcomes
Day-night rhythm in whole-body energy metabolism (energy expenditure)
Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm in whole-body energy metabolism (glucose oxidation)
Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm in whole-body energy metabolism (fat oxidation)
Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm in muscle protein levels of markers involved in molecular clock and mitochondrial metabolism.
Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm in muscle DNA of markers involved in molecular clock and mitochondrial metabolism.
Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm in muscle DNA involved in molecular clock and mitochondrial metabolism.
Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm in muscle mRNA markers involved in molecular clock and mitochondrial metabolism.
Time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Day-night rhythm of markers of normal day-night rhythm (cortisol)
Time frame: measured on day two, every two hours for 24 hours beginning at 08:00
Day-night rhythm of in markers of normal day-night rhythm (core body temperature)
Time frame: measured continuously for 24 hours on day two
Day-night rhythm of in markers of normal day-night rhythm (melatonin)
Time frame: measured on day two, every two hours for 24 hours beginning at 08:00
Day-night rhythm in serum glucose
Time frame: measured on day two, every two hours for 24 hours beginning at 08:00
Day-night rhythm in serum insulin
Time frame: measured on day two, every two hours for 24 hours beginning at 08:00
Day-night rhythm in serum free fatty acids (FFA)
Time frame: measured on day two, every two hours for 24 hours beginning at 08:00
Day-night rhythm in serum triglycerides
Time frame: measured on day two, every two hours for 24 hours beginning at 08:00
Day-night rhythm in serum cholesterol
Time frame: measured on day two, every two hours for 24 hours beginning at 08:00
Change in energy status of the heart between morning and evening
Time frame: Measured on first study day 5:30 PM (duration 45 minutes), second study day 7:30 AM (duration 45 minutes)
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 16 Aug 2019.
- Derived from this study: PubMed 38051503Harmsen JF, Kotte M, Habets I, Bosschee F, Frenken K, Jorgensen JA, de Kam S, Moonen-Kornips E, Cissen J, Doligkeit D, van de Weijer T, Erazo-Tapia E, Buitinga M, Hoeks J, Schrauwen P. Exercise training modifies skeletal muscle clock gene expression but not 24-hour rhythmicity in substrate metabolism of men with insulin resistance. J Physiol. 2024 Dec;602(23):6417-6433. doi: 10.1113/JP285523. Epub 2023 Dec 5.
- Derived from this study: PubMed 32659272Wefers J, Connell NJ, Fealy CE, Andriessen C, de Wit V, van Moorsel D, Moonen-Kornips E, Jorgensen JA, Hesselink MKC, Havekes B, Hoeks J, Schrauwen P. Day-night rhythm of skeletal muscle metabolism is disturbed in older, metabolically compromised individuals. Mol Metab. 2020 Nov;41:101050. doi: 10.1016/j.molmet.2020.101050. Epub 2020 Jul 11.
- Individual participant dataSharing planned: Undecided
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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.
Patrick Schrauwen, PhD principal investigator
Maastricht University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standardized living protocol 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 16 Aug 2019. 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?
Day-night rhythm in skeletal muscle mitochondrial respiration (time frame: measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03733743, which also lists 2 linked publications.
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 16 Aug 2019.