HIIT: A Proof-of-Concept Study

Study Overview
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Brief Summary
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This is a pilot randomized controlled trial of 20 physically inactive i-IFG adults aged 35-55 years with overweight or obesity. The investigators will test the effects of HIIT on fasting hyperglycemia, the pathophysiology of i-IFG, and continuous glucose monitoring (CGM) metrics compared with the control participants who will receive standard lifestyle recommendations. The research team will also examine the feasibility of conducting the study procedures and assess the acceptability of HIIT intervention.

Detailed Description
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This is a Proof-of-Concept 1:1 parallel-group RCT of 20 physically inactive i-IFG participants aged 35-55 years with overweight or obesity. Interested individuals will be invited to come in a fasting state (8-10 hours of overnight fasting). They will be administered a short questionnaire with the eligibility criteria and the Seven- Day Physical Activity Recall (7 Day PAR), and undergo height and weight measurements. On the first day of the intervention, each participant will be fitted with a Dexcom G6 Pro CGM sensor beneath the skin by trained study staff. Participants will wear the device 2 days before the first exercise session (baseline) and then will wear the device for 10 days. The CGM system includes a sensor, a transmitter, and a receiver. The sensor measures the interstitial fluid glucose levels every 5 minutes, and the transmitter sends glucose data wirelessly from the sensor to the receiver. Participants will undergo measurements at baseline and after 4 weeks of intervention. Height and weight will be measured using measuring scales based on standard protocols. Early-phase insulin secretion will be measured using the validated and widely used insulinogenic index ([I30-I0]/[G30-G0]) with insulin and glucose levels at 0 and 30 min of the OGTT. Hepatic IR will be assessed using HIRI (glucose0-30[AUC] insulin0-30[AUC]), which correlates strongly with the direct measure of hepatic IR from euglycemic insulin clamps. After 4 weeks, intervention acceptability will be assessed using a short questionnaire with questions about the use of Spin bikes, timing, frequency and the number of exercise sessions, motivation to participate in the intervention, facilitators and barriers to participate in the intervention, and satisfaction with the intervention.

Official Title
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Effect of High-Intensity Interval Training on Fasting Hyperglycemia in People With Isolated Impaired Fasting Glucose: A Proof-of-Concept Study

Conditions
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Obesity

Intervention / Treatment
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* Other: High-Intensity Interval Training
* Other: Standard exercise recommendations
* Device: Continuous glucose monitoring (CGM) (Dexcom G6 Pro CGM sensor)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: males and females of any race or ethnicity aged 35-55 years; overweight (body mass index [BMI] 25.0 to <30.0 kg/m2)24 or obese (BMI ≥30.0 kg/m2); history of prediabetes; and physically inactive (<150 min of moderate-intensity or <75 min of vigorous-intensity aerobic physical activity/week) Exclusion Criteria: history of diabetes; no exercise training in the past 6 months; pregnant women; smokers; taking glucose-lowering drugs (e.g., metformin); and those with chronic illnesses (e.g.,stroke). Individuals satisfying the eligibility criteria will undergo a 3-step OGTT (0, 30, 120 min), and those diagnosed with i-IFG (FPG 110-125 mg/dl and 2-hr PG <140 mg/dl) will be recruited to the study.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group<br>Intervention participants will perform 12 sessions (3 sessions per week on alternate days) of supervised HIIT (cycling bouts eliciting 50-85% maximal heart rate) over 4 weeks. HIIT with Spin sessions will include a 5-min warm-up, then an interval-based workout phase with steady up-tempo cadences, sprints, and climbs (interspersed with recovery periods), followed by a 5-min cool down. | Other: High-Intensity Interval Training<br>* HIIT with Spin sessions that will include a 5-min warm-up, then an interval-based workout phase with steady up-tempo cadences, sprints, and climbs (interspersed with recovery periods), followed by a 5-min cool down. All participants will wear Polar H10 chest strap heart rate sensors to ensure adequate intensity throughout each session and be instructed daily on their target heart rate range, computed using the Karvonen method. Phone calls will be made to the participants a day before each session to remind them about their scheduled session. Also, a log of the number of exercise sessions attended by each participant will be kept, which will be reviewed regularly to ensure high compliance with the intervention.<br>* Other names: HIIT intervention;Device: Continuous glucose monitoring (CGM) (Dexcom G6 Pro CGM sensor)<br>* The CGM system includes a sensor, a transmitter, and a receiver. The sensor measures the interstitial fluid glucose levels every 5 minutes, and the transmitter sends glucose data wirelessly from the sensor to the receiver. Participants will undergo measurements at baseline and after 4 weeks of intervention.<br>* Other names: Dexcom G6 Pro CGM sensor;|
| Active Comparator: Control Group<br>Control participants will receive standard exercise recommendations (≥150 min of moderate-intensity physical activity per week distributed throughout the week with a minimum frequency of thrice a week). | Other: Standard exercise recommendations<br>* Recommendation is ≥150 min of moderate-intensity physical activity per week distributed throughout the week with a minimum frequency of thrice a week.<br>Device: Continuous glucose monitoring (CGM) (Dexcom G6 Pro CGM sensor)<br>* The CGM system includes a sensor, a transmitter, and a receiver. The sensor measures the interstitial fluid glucose levels every 5 minutes, and the transmitter sends glucose data wirelessly from the sensor to the receiver. Participants will undergo measurements at baseline and after 4 weeks of intervention.<br>* Other names: Dexcom G6 Pro CGM sensor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting plasma glucose (FPG) from baseline | Fasting plasma glucose will be compared at baseline and 4 weeks post-intervention between the intervention and control participants. | Baseline, 4 weeks post-intervention | 
| Change in insulinogenic index from baseline | Early-phase insulin secretion will be measured using the insulinogenic index ([I30-I0]/[G30-G0]) with insulin and glucose levels at 0 and 30 min of the OGTT. Results will be compared between the intervention and control participants. | Baseline, 4 weeks post-intervention | 
| Change in hepatic insulin resistance index (HIRI) from baseline | Hepatic insulin resistance (IR) will be assessed using HIRI (glucose 0-30[AUC] x insulin 0-30[AUC]). Results will be compared between study groups. | Baseline, 4 weeks post-intervention | 
| Change in weight from baseline | Weight will be compared between intervention and control group. | Baseline, 4 weeks post-intervention | 
| Change in BMI from baseline | BMI will be compared between intervention and control group. | Baseline, 4 weeks post-intervention | 
| Time in range (TIR) of normoglycemia (70 to <110 mg/dl) overnight | Time in range (TIR) of normoglycemia (70 to <110 mg/dl) overnight measured by CGM will be compared between the intervention and control group. | 4 weeks post-intervention | 
| Change in mean fasting glucose on post-exercise day | Change in mean fasting glucose (one hour mean following 8-10 hours of fasting) on post- exercise day will be compared between study groups. | Baseline, 4 weeks post-intervention | 
| Change in coefficient of variation in glucose levels | Coefficient of variation in glucose levels (overnight and overall) will be compared between study groups. | Baseline, 4 weeks post-intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Intervention Acceptability Questionnaire score | Intervention Acceptability Questionnaire will be measured using a Likert scale of 1-5: 1, Strongly disagree; 2, Disagree; 3, Neutral; 4, Agree; 5, Strongly agree. The minimum score will be 10 and the maximum score will be 50. Higher scores mean a better intervention acceptability. | Baseline, 4 weeks post-intervention |