Restoring 24-hour Substrate Rhythmicity to Improve Glycemic Control by Timing of Lifestyle Factors

NCT05123963 | Recruiting

• 1 other identifier: MP-31-2021-4011
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Exercise is well-known to improve skeletal muscle energy metabolism and is an established intervention to improve muscle insulin sensitivity and to counter the development of type 2 diabetes (T2D). However, given the 24h rhythmicity in substrate metabolism previously observed in healthy, lean men and the lack of such rhythmicity in men with insulin-resistance, the investigator hypothesize that appropriate timing of exercise training can maximize the metabolic health effects of exercise. Indeed, a preliminary study in humans revealed that afternoon high-intensity interval training (HIIT) exercise was more effective than morning exercise in improving 24h blood glucose levels in men with T2D. Another recent study in mice showed that the time of day is a critical factor in augmenting the beneficial effects of exercise on the skeletal muscle metabolome as well as on whole-body energy homeostasis. However, human studies that specifically target the impact of timing of exercise training on glucose homeostasis and metabolic health are scarce and the potential underlying mechanisms largely unknown. The overarching goals of this project is to improve 24-hour rhythmicity of metabolism in men and women with prediabtes by appropriate timing of exercise and to assess its effect on metabolic health and immune response. Acute and prolonged exercise interventions timed in the morning vs late afternoon will be carried out in individuals with prediabetes to determine whether acute exercise in the afternoon and prolonged exercise training in the afternoon can improve peripheral insulin sensitivity, compared to exercise in the morning, and positively affect adipose tissue dietary fatty acid storage and partitioning of dietary fatty acids in skeletal muscles.

Conditions

Prediabetic State

Keywords

Postprandial metabolism; High-intensity interval training

Outcome Measures

Primary Outcomes (4)

• Change in Adipose tissue dietary fatty acid (DFA) partitioning

  Determined using oral administration of \[18F\]-Fluoro-6-Thia-Heptadecanoic Acid (FTHA) during whole-body acquisition

  Measured 180 minutes, 240 minutes, 300 minutes and 360 minutes after liquid meal at baseline visit, 18-24hours after acute exercise bout and >48hours after final exercise bout (after 12 week intervention).

• Change in lean organ (heart, liver, skeletal muscle) DFA partitioning

  Determined using oral administration of \[18F\]-Fluoro-6-Thia-Heptadecanoic Acid (FTHA) during whole-body acquisition

  Measured 180 minutes, 240 minutes, 300 minutes and 360 minutes after liquid meal at baseline visit, 18-24hours after acute exercise bout and >48hours after final exercise bout (after 12 week intervention).

• Change in skeletal muscle ATP fluxes in vivo

  Determined using phosphorus-31 magnetic resonance spectroscopy.

  Measured 170 minutes before and 30 minutes following liquid meal at baseline visit, 18-24hours after acute exercise bout and >48hours after final exercise bout (after 12 week intervention).

• Change in glucose control.

  Determined using continuous glucose monitoring and repeated blood samples obtained during metabolic visit.

  Measured continuously 2-3 days before and 2-3 days after first and final exercise session, after 12-week exercise intervention.

Secondary Outcomes (11)

• Change in adipose tissue nonesterified fatty acid (NEFA) metabolism.

  Measured 150 minutes before and 60 minutes following liquid meal at baseline visit, 18-24hours after acute exercise bout and >48hours after final exercise bout (after 12 week intervention).

• Change in lean organ (heart, liver, skeletal muscle) NEFA metabolism.

  Measured 150 minutes before and 60 minutes following liquid meal at baseline visit, 18-24hours after acute exercise bout and >48hours after final exercise bout (after 12 week intervention).

• Change in insulin sensitivity

  Measured every 60 minutes following liquid meal at baseline visit, 18-24hours after acute exercise bout and >48hours after final exercise bout (after 12 week intervention).

• Change in dietary fatty acid oxidation

  Measured every 60 minutes following liquid meal at baseline visit, 18-24hours after acute exercise bout and >48hours after final exercise bout (after 12 week intervention).

• Change in total substrate utilisation

  Measured every 60 minutes following liquid meal at baseline visit, 18-24hours after acute exercise bout and >48hours after final exercise bout (after 12 week intervention).

Study Arms (2)

Morning exercise

ACTIVE COMPARATOR

Participant to perform high-intensity interval training in the morning (\~9 am)

Behavioral: High-intensity interval training

Afternoon exercise

EXPERIMENTAL

Participant to perform high-intensity interval training in the morning (\~4 pm)

Behavioral: High-intensity interval training

Interventions

High-intensity interval training BEHAVIORAL

3 times per week high-intensity interval training (HIIT) on a cycle ergometer for 12 weeks.

Afternoon exercise; Morning exercise

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pre-diabetes:
• Fasting plasma glucose: 6.1 to 6.9 mmol/L or
• hour plasma glucose post 75g OGTT: 7.8 to 11.0 mmol/L and
• HbA1c: 6.0 to 6.4%
• or Insulin resistant: glucose clearance rate ≤ 360 ml/kg/min as determined using the Oral Glucose Insulin Sensitivity Index at Time 120 min.
• BMI \> 25 kg/m2
• To be willing and able to adhere to the specifications of the protocol;
• To have signed an informed consent document indicating that they understood the purpose of and procedures required for the study and were willing to participate in the study.

You may not qualify if:

• overt cardiovascular disease as assessed by medical history, physical exam, and abnormal ECG
• Treatment with any drug known to affect lipid or carbohydrate metabolism, except statins (to be stopped 3 weeks prior to study A), metformin or anti-hypertensive drugs (to be stopped 7 days prior to the studies);
• presence of liver or renal disease other than uncomplicated NASH or mild isolated proteinuria; uncontrolled thyroid disorder;
• Uncontrolled severe hypertension, systolic pressure ≥ 180 mm Hg or diastolic pressure ≥ 110 mm Hg;
• History of ischemic heart disease, tachyarrhythmia, QT interval prolongation, risk factors for torsade de pointes (eg hypokalemia), or taking any medication known to prolong the QT interval;
• History of serious gastrointestinal disorders (malabsorption, peptic ulcer, gastroesophageal reflux requiring surgery, etc.);
• Presence of a pacemaker;
• Having undergone a PET study or CT scan in the past year;
• Any contraindication to stopping statins for 3 months and stopping an anti-hypertensive medication and metformin for 7 days;
• smoking (\>1 cigarette/day) and/or consumption of \>2 alcoholic beverages per day;
• No blood donation two month prior the study;
• prior history or current fasting plasma cholesterol level \> 7 mmol/l or fasting TG \> 6 mmol/l.

Sponsors & Collaborators

• Université de Sherbrooke: lead
• University of Calgary: collaborator
• University of Waterloo: collaborator
• Laval University: collaborator
• Wageningen University: collaborator
• Maastricht University Medical Center: collaborator
• Leiden University Medical Center: collaborator
• McMaster University: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator

Study Sites (1)

Centre de recherche du CHUS

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

MeSH Terms

Conditions

Prediabetic State

Interventions

High-Intensity Interval Training

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Denis P. Blondin, PhD

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frédérique Frisch

CONTACT

819-346-1110; frederique.frisch@usherbrooke.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two randomized groups in parallel (Exercise training in the morning versus exercise training in the evening). In each group, the protocol will be carried out as a within-subject in which each subject will serve as his/her own control (before/after acute or prolonged exercise).

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: November 17, 2021
• Study Start: September 15, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 30, 2026
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)