HIIT in Isolated IFG: A Proof-of-Concept Study

High-Intensity Interval Training for Individuals With Isolated Impaired Fasting Glucose: A Proof-of-Concept Study

This pilot randomized controlled trial will involve 34 physically inactive adults aged 35-65 years with overweight or obesity and isolated impaired fasting glucose (i-IFG). The study aims to assess the feasibility of recruiting and retaining participants, implementing study procedures, and evaluating the acceptability of a high-intensity interval training (HIIT) intervention. Additionally, it will investigate the preliminary efficacy of HIIT in reducing fasting plasma glucose levels and addressing the pathophysiology of i-IFG.

Study Overview

• Status: Withdrawn
• Conditions: Isolated Impaired Fasting Glucose
• Intervention / Treatment: Device: Continuous glucose monitoring (CGM) (Dexcom G6 Pro CGM sensor); Behavioral: High-intensity interval training and eucaloric diet; Behavioral: No intense physical activity and eucaloric diet

Detailed Description

This 1:1 proof-of-concept randomized controlled trial (RCT) will involve 34 physically inactive adults aged 35-65 years who are overweight or obese and have isolated impaired fasting glycemia (i-IFG). Potentially eligible individuals identified through Emory's MyChart electronic health care records system will undergo initial screening via phone calls. Individuals meeting the eligibility criteria will be invited to the Georgia Clinical and Translational Science Alliance at Emory University Hospital in Atlanta for further assessment. During their visit, participants will complete questionnaires, undergo an oral glucose tolerance test, and provide blood samples for insulin. Individuals identified with i-IFG will be randomized into the intervention or control groups.

Individuals assigned to the intervention group will participate in supervised high-intensity interval training (HIIT) sessions using stationary Spin cycle ergometers, in groups of five or fewer. They will wear continuous glucose monitoring (CGM) devices for 10 days before the intervention, throughout the 8-week intervention period, and for 10 days post-intervention. The intervention will be conducted three times a week for eight weeks at the Aerobic Exercise Laboratory in the Rehabilitation Hospital at Emory University. Control participants will be instructed to refrain from engaging in intense physical activities during the study period and will also wear CGM devices for the same duration. All participants will receive instructions to maintain a eucaloric diet throughout the study.

At baseline and after eight weeks, all participants will undergo physical measurements (anthropometrics, blood pressure, and body composition) as well as biochemical measurements (glucose and insulin levels). Additionally, participants in the intervention group will be invited to participate in qualitative in-depth interviews both before and after the HIIT intervention and will complete an intervention acceptability questionnaire upon completion.

The primary outcomes include feasibility metrics, measures of intervention feasibility, acceptability, and appropriateness, and participants' experiences, perceptions, and satisfaction with the HIIT intervention, as well as facilitators and barriers to participation. Secondary outcomes include: 1) Between-group differences in changes from baseline to 8 weeks in mean fasting plasma glucose and insulin levels, indices of β-cell function and insulin resistance, and physical measurements; and 2) CGM metrics: a) Between-group differences in the proportion of time and mean time spent in nocturnal (00:00-06:00) [58] normoglycemia (60 to <100 mg/dl) during the 8-week intervention period and the 10 days following the intervention; b) Within-participant differences in the proportion of time and mean time spent in nocturnal (00:00-06:00) normoglycemia (60 to <100 mg/dl) between exercise and non-exercise days during the 8-week intervention period.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Males and females aged 35-65 years
2. Any race or ethnicity
3. BMI ≥25 kg/m2 (≥23 kg/m2 if Asian decent)
4. Physically inactive (<150 min of moderate-intensity or <75 min of vigorous-intensity aerobic physical activity/week)
5. Will be residing in the same location until completion of the study
6. Isolated impaired fasting glucose on the OGTT: FPG 100-125 mg/dl and 2-hr plasma glucose <140 mg/dl

Exclusion criteria:

1. History of diabetes
2. Regular exercise training in the past 6 months
3. Enrolled in weight loss programs in the past 6 months
4. Following a specific diet (e.g., ketogenic, Mediterranean)
5. Pregnant women
6. Breastfeeding
7. Smokers
8. Taking medications known to affect glucose tolerance (e.g., steroids)
9. Taking beta-blockers and calcium channel blockers
10. Taking weight loss medications
11. Underwent bariatric surgery
12. Anemia
13. History of chronic illnesses (e.g., stroke)

Individuals satisfying the eligibility criteria will undergo an OGTT (0, 30, 120 min), and those diagnosed with i-IFG (FPG 100 or 110-125 mg/dl and 2-hr PG <140 mg/dl) will be recruited to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; Intervention participants will complete 24 supervised high-intensity interval training (HIIT) sessions over 8 weeks, with 3 sessions per week on alternate days. Each HIIT session will consist of a 5-minute warm-up, followed by an interval-based workout phase that includes steady up-tempo cadences, sprints, and climbs, interspersed with recovery periods. The session will conclude with a 5-minute cooldown. The workout sessions will initially last 20 minutes and will progressively increase in time based on participants' tolerance and instructor recommendations. Intensity will start at 75% of the estimated maximal heart rate reserve and will increase by 5% weekly, as tolerated and/or deemed necessary by the instructor, over the 8-week intervention period. Participants will receive instructions to maintain a eucaloric diet throughout the study.	Device: Continuous glucose monitoring (CGM) (Dexcom G6 Pro CGM sensor); The continuous glucose monitoring (CGM) system comprises a sensor, a transmitter, and a receiver. The sensor measures interstitial fluid glucose levels every 5 minutes, and the transmitter wirelessly sends this glucose data to the receiver. Both intervention and control participants will wear the CGM device in a blinded mode for 10 days before starting the intervention, throughout the 8-week intervention period, and for 10 days post-intervention.; Other Names: Dexcom G6 Pro CGM sensor; Behavioral: High-intensity interval training and eucaloric diet; Intervention participants will complete 24 supervised high-intensity interval training (HIIT) sessions over 8 weeks, with 3 sessions per week on alternate days. Each HIIT session will consist of a 5-minute warm-up, followed by an interval-based workout phase that includes steady up-tempo cadences, sprints, and climbs, interspersed with recovery periods. The session will conclude with a 5-minute cooldown. The workout sessions will initially last 20 minutes and will progressively increase in time based on participants' tolerance and instructor recommendations. Intensity will start at 75% of estimated maximal heart rate reserve and will increase by 5% weekly, as tolerated and/or deemed necessary by the instructor, over the 8-week intervention period. Participants will receive instructions to maintain a eucaloric diet throughout the study.; Other Names: HIIT intervention
Active Comparator: Control Group; Control participants will be instructed to refrain from engaging in intense physical activities during the study period. They will also receive instructions to maintain a eucaloric diet throughout the study.	Device: Continuous glucose monitoring (CGM) (Dexcom G6 Pro CGM sensor); The continuous glucose monitoring (CGM) system comprises a sensor, a transmitter, and a receiver. The sensor measures interstitial fluid glucose levels every 5 minutes, and the transmitter wirelessly sends this glucose data to the receiver. Both intervention and control participants will wear the CGM device in a blinded mode for 10 days before starting the intervention, throughout the 8-week intervention period, and for 10 days post-intervention.; Other Names: Dexcom G6 Pro CGM sensor; Behavioral: No intense physical activity and eucaloric diet; Control participants will be instructed to refrain from engaging in intense physical activities during the study period. They will also receive instructions to maintain a eucaloric diet throughout the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate in %	No. of individuals responded to the invitation/No. of individuals invited.	Baseline
Screening yield in %	No. of individuals diagnosed with i-IFG/No. of individuals screened.	Baseline
Enrolment rate in %	No. of individuals enrolled/No. of individuals diagnosed with i-IFG.	Baseline
Time to enrollment (mins)	Average time taken from sending the invitation to enrolling one participant in the trial.	Baseline
Intervention compliance in %	No. of HIIT sessions attended/Total no. of HIIT sessions.	8 weeks
Program costs (USD)	Includes screening cost, cost of procedures, intervention cost, participant incentives, and other costs.	From baseline to 8 weeks
Staff time (mins)	Time spent screening and recruiting participants, time spent delivering the intervention, time spent making phone calls to participants, time spent implementing the study procedures, and time spent on baseline and follow-up assessments.	From baseline to 8 weeks
Retention rate in %	No. of participants attended follow-up visits/No. of participants enrolled.	8 weeks
Feasibility of Intervention Measure (FIM) score	The FIM scale will evaluate the feasibility of the intervention, encompassing questions regarding its implementability, possibility, doability, and ease of use. Responses to the questions in the questionnaire will be recorded on a Likert scale of 1 to 5. The mean total score will be calculated by combining the individual Likert points. Higher scores on the FIM scale indicate greater intervention feasibility.	8 weeks
Theoretical Framework of Acceptability (TFA) score	The acceptability of the intervention will be assessed through the Theoretical Framework of Acceptability (TFA) questionnaire, which explores affective attitude, burden, ethicality, perceived effectiveness, intervention coherence, self-efficacy, opportunity costs, and general acceptability.	8 weeks
Intervention Appropriate Measure (IAM) score	The Intervention Appropriate Measure (IAM) will evaluate the appropriateness of the intervention, including questions about its fittingness, suitability, applicability, and alignment with participants' needs.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting plasma glucose (mg/dl)	Change in fasting plasma glucose from baseline to 8 weeks will be compared between study groups.	8 weeks
Fasting insulin (µU/ml)	Change in fasting insulin from baseline to 8 weeks will be compared between study groups.	8 weeks
Weight in kg	Weight will be measured using a digital weighing scale (Welch Ally-Scale-Tronix, NY, USA) with precision to the nearest 0.1 kg. The change in weight from baseline to 8 weeks will be compared between the intervention and control groups.	8 weeks
BMI in kg/m2	Change in BMI from baseline to 8 weeks will be compared between study groups.	8 weeks
Waist circumference in cm	Change in waist circumference from baseline to 8 weeks will be compared between study groups.	8 weeks
Waist-to-hip ratio	Change in waist-to-hip ratio from baseline to 8 weeks will be compared between study groups.	8 weeks
Systolic blood pressure in mmHg	Change in systolic BP from baseline to 8 weeks will be compared between study groups.	8 weeks
Diastolic blood pressure in mmHg	Change in diastolic BP from baseline to 8 weeks will be compared between study groups.	8 weeks
Insulinogenic index (IGI)	IGI is a measure of early-phase insulin secretion.	8 weeks
Oral Disposition Index (DIO)	DIO is a measure of ß-cell function.	8 weeks
Homeostatic Model Assessment of ß-cell function (HOMA-B)	HOMA-B is a measure of ß-cell function.	8 weeks
Matsuda index	Matsuda index is a measure of insulin resistance.	8 weeks
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	HOMA-IR is a measure of insulin resistance.	8 weeks
Hepatic Insulin Resistance Index (HIRI)	HIRI is a measure of hepatic insulin resistance.	8 weeks
Muscle Insulin Sensitivity Index (MISI)	MISI is a measure of muscle insulin resistance.	8 weeks
Fat percent (%)	Fat percent will be obtained by bioimpedance analysis.	8 weeks
Fat mass (kg)	Fat mass will be obtained by bioimpedance analysis.	8 weeks
Muscle mass (kg)	Muscle mass will be obtained by bioimpedance analysis.	8 weeks
Visceral adipose tissue mass (kg)	Visceral adipose tissue mass will be obtained by bioimpedance analysis.	8 weeks
CGM metric: Proportion of time spent in nocturnal (00:00-06:00) normoglycemia (60 to <100 mg/dl)	Proportion of time spent in nocturnal (00:00-06:00) normoglycemia (60 to <100 mg/dl) during the 8-week intervention period.	From baseline to 8 weeks
CGM metric: Proportion of time spent in nocturnal (00:00-06:00) normoglycemia (60 to <100 mg/dl)	Proportion of time spent in nocturnal (00:00-06:00) normoglycemia (60 to <100 mg/dl) during the 10 days following the intervention.	10 days following the intervention
CGM metric: Mean time spent in nocturnal (00:00-06:00) normoglycemia (60 to <100 mg/dl)	Mean time spent in nocturnal (00:00-06:00) normoglycemia (60 to <100 mg/dl) during the 8-week intervention period.	From baseline to 8 weeks
CGM metric: Mean time spent in nocturnal (00:00-06:00) normoglycemia (60 to <100 mg/dl)	Mean time spent in nocturnal (00:00-06:00) normoglycemia (60 to <100 mg/dl) during the 10 days following the intervention.	10 days following the intervention

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Sathish Thirunavukkarasu, PhD, Emory University

Publications and helpful links

General Publications

• Thirunavukkarasu S, Ziegler TR, Weber MB, Staimez L, Lobelo F, Millard-Stafford ML, Schmidt MD, Venkatachalam A, Bajpai R, El Fil F, Prokou M, Kumar S, Tapp RJ, Shaw JE, Pasquel FJ, Nocera JR. High-Intensity Interval Training for Individuals With Isolated Impaired Fasting Glucose: Protocol for a Proof-of-Concept Randomized Controlled Trial. JMIR Res Protoc. 2025 Feb 20;14:e59842. doi: 10.2196/59842.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: November 21, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; Prediabetes; High-intensity interval training; Isolated impaired fasting glucose
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Prediabetic State; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Physical Conditioning, Human; Exercise; Blood Chemical Analysis; Clinical Chemistry Tests; Diagnostic Techniques, Endocrine; Monitoring, Physiologic; High-Intensity Interval Training; Continuous Glucose Monitoring
• Other Study ID Numbers: STUDY00005855; UL1TR002378 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No