Timing Exercise Training as Strategy to Improve Insulin Sensitivity and Substrate Metabolism in Men and Woman With Pre-diabetes (Timed Training)

• ClinicalTrials.gov Identifier: NCT06014684
• Recruitment Status: Recruiting
• First Posted: August 28, 2023
• Last Update Posted: August 28, 2023
• Sponsor: Maastricht University Medical Center
• Information provided by (Responsible Party): Maastricht University Medical Center

Study Description

Brief Summary:

n a retrospective analysis of an exercise training program performed either in the morning or afternoon, we found that the afternoon training group improved their peripheral insulin sensitivity and fasting plasma glucose levels to a greater extent than the morning group. However, underlying mechanisms are unclear.

The main objective of this study is to determine whether prolonged exercise training in the afternoon (15:00-17:00 PM) differs from exercise training in the morning (07:00-09:00 AM) in improving insulin sensitivity in individuals with pre-diabetes, and to investigate its underlying mechanisms.

Condition or disease	Intervention/treatment	Phase
Pre-diabetes; Overweight and Obesity	Behavioral: Timing of exercise	Not Applicable

Detailed Description:

Rationale: Various metabolic processes, including resting metabolic rate, insulin sensitivity and insulin secretion, follow a recurring 24-hour cycle. These rhythms are shown to be disturbed in in pre-diabetes volunteers compared to young healthy volunteers. In a retrospective analysis of an exercise training program performed either in the morning or afternoon, we found that the afternoon training group improved their peripheral insulin sensitivity and fasting plasma glucose levels to a greater extent than the morning group. However, underlying mechanisms are unclear.

Objective: The main objective of this study is to determine whether prolonged exercise training in the afternoon (15:00-17:00 PM) differs from exercise training in the morning (07:00-09:00 AM) in improving insulin sensitivity in individuals with pre-diabetes, and to investigate its underlying mechanisms.

Study design: The present study is a randomized double arm longitudinal intervention study in a pre and post design.

Study population: 24 pre-diabetic individuals (men and postmenopausal women aged 40 - 75 years and with BMI ≥ 25 and ≤ 38 kg/m2) will complete this study (12 participants in the morning training group and 12 participants in the afternoon training group). From experience with similar studies, we estimate a drop-out rate of 20% and a screening failure of 70% (because individuals often do not know they are pre-diabetic). This results in maximally 30 participants that have to be included and 100 participants that have to be screened (maximally).

Intervention (if applicable): Participants will perform a 12-weeks supervised high intensity interval training (HIIT) program with three ~30 min exercise sessions per week. Participants will be randomly assigned to the morning or afternoon training time. To assess the outcomes, participants will come to the university for a 43h measurement period both before and after the 12-week training program.

Main study parameters/endpoints: The primary study endpoint is peripheral insulin sensitivity measured via a 2-step hyperinsulinemic-euglycemic clamp. The secondary outcomes are 24h energy and substrate metabolism. Exploratory outcomes are body composition, intrahepatic lipid content and composition, hepatic insulin sensitivity, hepatic glycogen levels, maximal aerobic capacity, skeletal muscle oxidative capacity, visceral and subcutaneous adipose tissue volume, sleeping metabolic rate, blood glucose levels (continuously measured over 7days) and immune responses.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Timing Exercise Training as Strategy to Improve Insulin Sensitivity and Substrate Metabolism in Men and Woman With Pre-diabetes
• Actual Study Start Date: July 13, 2023
• Estimated Primary Completion Date: March 1, 2026
• Estimated Study Completion Date: March 1, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: AM exercise; HIIT program performed between 07:00-09:00 AM	Behavioral: Timing of exercise; High Intensity Interval Training (HIIT) program for 12 weeks (3 per week/36 sessions in total)
Experimental: PM exercise; HIIT program performed between 15:00-17:00 PM	Behavioral: Timing of exercise; High Intensity Interval Training (HIIT) program for 12 weeks (3 per week/36 sessions in total)

Outcome Measures

Primary Outcome Measures :

1. Peripheral Insulin sensitivity [ Time Frame: measured before and after the 12 weeks training program ]
   Glucose disposal rate under high insulin concentrations during the second step of the 2-step hyperinsulinemic-euglycemic clamp.

Secondary Outcome Measures :

1. 24h whole body energy expenditure [ Time Frame: measured before and after the 12 weeks training program ]
   energy expenditure as measured by a 24h stay in the respiration chamber
2. 24h substrate metabolism [ Time Frame: measured before and after the 12 weeks training program ]
   24h substrate metabolism as measured by a 24h stay in the respiration chamber

Other Outcome Measures:

1. Body composition by Dual Energy X-ray Absorptiometry (DEXA) [ Time Frame: measured before and after the 12 weeks training program ]
   fat-free mass (kg and percentage)
2. Body composition by Dual Energy X-ray Absorptiometry (DEXA) [ Time Frame: measured before and after the 12 weeks training program ]
   fat mass (kg and percentage)
3. Intrahepatic lipid content and composition [ Time Frame: measured before and after the 12 weeks training program ]
4. Hepatic glycogen levels [ Time Frame: measured before and after the 12 weeks training program ]
5. VO2 max cycling test [ Time Frame: measured before and after the 12 weeks training program ]
   measurement of participants' maximal aerobic capacity, absolute (L/min) and relative (ml/min/kg)
6. Skeletal muscle oxidative capacity [ Time Frame: measured before and after the 12 weeks training program ]
   Ex vivo high-resolution respirometry using a two chamber Oxygraph (OROBOROS Instruments) will be performed. Multiple substrate/inhibitor titration protocols will be applied to extensively characterize the mitochondrial capacity of skeletal muscle fibers
7. Sleeping metabolic rate [ Time Frame: measured before and after the 12 weeks training program ]
8. Blood glucose levels measured continuously over 7 days. [ Time Frame: measured before and at the end the 12 weeks training program ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Aged 40-75 years.
• Body mass index (BMI) ≥25 kg/m2
• Male, or postmenopausal (at least 1 year post cessation of menses) female

• Pre-diabetes 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
  • ImpairedFastingGlucose(IFG):Fastingplasmaglucose≥6.1mmol/land≤6.9 mmol/l
  • Insulin Resistance: glucose clearance rate ≤ 360 mL/kg/min, as determined during the OGTT using OGIS120.
  • HbA1cof5.7-6.4%

Exclusion Criteria:

• Type 2 diabetes
• Patients with active congestive heart failure and and/or severe renal and or liver insufficiency
• Uncontrolled hypertension
• Any contra-indication for MRI scanning
• Alcohol consumption of >3 servings per day for man and >2 servings per day for woman
• Smoking
• Unstable body weight (weight gain or loss > 5kg in the last 3 months)
• Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator which would possibly hamper our study results.
• Medication use known to hamper subject's safety during the study procedures.
• Subjects who do not want to be informed about unexpected medical findings.
• Men: Hb <8.0 mmol/L, Women: Hb <7.0 mmol/l
• Heavily varying sleep-wake rhythm (i.e. night shift work and travels across time zones).
• Significant food allergies/intolerance (seriously hampering study meals)
• Blood donation during or within 2 months prior to the study

Contacts and Locations

Contacts

Contact: Ivo Habets, MSc; +31 88 388 7287; i.habets@maastrichtuniversity.nl

Contact: Soraya de Kam, MSc; soraya.dekam@maastrichtuniversity.nl

Locations

Netherlands

Maastricht University; Recruiting

Maastricht, Limburg, Netherlands, 6229 ER

Contact: Ivo Habets, MSc +31 88 388 7287 i.habets@maastrichtuniversity.nl

Sponsors and Collaborators

Maastricht University Medical Center

More Information

• Responsible Party: Maastricht University Medical Center
• ClinicalTrials.gov Identifier: NCT06014684
• Other Study ID Numbers: NL83421.068.22
• First Posted: August 28, 2023
• Last Update Posted: August 28, 2023
• Last Verified: July 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Overweight; Insulin Resistance; Prediabetic State; Glucose Intolerance; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Hyperinsulinism; Hyperglycemia