Exercise, Chronotype, and Prediabetes

NCT07389005 | Not Yet Recruiting

• 1 other identifier: REALIGN
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to find out whether exercising at the right time of day, based on a person's natural body clock, leads to greater health benefits in people living with prediabetes. The main question it aims to answer is whether doing a single session of exercise in the morning or in the evening affects how the body handles sugar differently in adults with prediabetes who have an extreme natural body clock. This will be done by comparing three conditions (no-exercise, morning exercise, and evening exercise) within the same participant. Each condition will be tested on a different day, with at least 14 days between the test days. During the no-exercise test days, participants will come to the study centre and will only be allowed to do sedentary activities (e.g. office work, reading, or screen time). During the morning exercise test days, participants will perform an exercise session at 9:00 am that involves short periods of very hard effort followed by short rest periods. Whereas for the evening exercise test days, the same type of exercise will be performed at 5:00 pm.

Conditions

Prediabetes; Overweight , Obesity

Keywords

Prediabetes; Overweight; Obesity; Exercise; Chronotype

Outcome Measures

Primary Outcomes (1)

• Insulin sensitivity

  Effect of timed exercise on insulin sensitivity assessed using insulin sensitivity index (reported as M-value: mg x kg-1 x min-1) during an hyperinsulinemic-euglycemic clamp

  12 to 24 hours post-exercise intervention

Secondary Outcomes (12)

• Skeletal muscle metabolites

  12 to 24 hours post-exercise intervention

• Skeletal muscle clock genes

  12 to 24 hours post-exercise intervention

• Adipose tissue metabolites

  12 to 24 hours post-exercise intervention

• Adipose tissue clock genes

  12 to 24 hours post-exercise intervention

• Hepatic glycogen content assessed using 13C Magnetic Resonance Spectroscopy

  Post-dinner on exercise day

Other Outcomes (15)

• Liver lipid content measured using ¹H/³¹P Magnetic Resonance Spectroscopy

  Baseline assessment

• Skeletal muscle lipid content measured using ¹H/³¹P Magnetic Resonance Spectroscopy

  Baseline assessment

• Body composition expressed as fat mass (kg and %) and fat-free mass (kg) assessed using Bodpod and Bioelectrical Impedance

  Baseline assessment

Study Arms (3)

AM exercise

EXPERIMENTAL

Behavioral: Timing of exercise

Behavioral: Timing of exercise

PM exercise

EXPERIMENTAL

Behavioral: Timing of exercise

Behavioral: Timing of exercise

Control

ACTIVE COMPARATOR

Behavioral: Control

Behavioral: Control

Interventions

Timing of exercise BEHAVIORAL

An acute exercise bout of cycling performed in the morning at 9 AM

AM exercise

Control BEHAVIORAL

No exercise

Control

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide signed and dated written informed consent prior to any study specific procedures
• Adult men and women aged between more than 18 and ≤ 75 years
• Body mass index (BMI) of 25 - 35 kg/m2
• Stable weight (no weight loss or gain \> 3 kg in the past 3 months)
• Pre-diabetes defined as an isolated impaired glucose tolerance or a combination of impaired glucose tolerance and impaired fasting glucose (values are based on the American Diabetes Association (ADA):
• impaired glucose tolerance (plasma glucose 140 mg/dL to 199 mg/dL, 120 minutes after consumption of 75g of glucose)
• impaired fasting glucose (fasting plasma glucose 100 mg/dL to 125 mg/dL)
• Morning (Morningness-Eveningness Questionnaire \[MEQ\] score ≥ 59) or evening (MEQ score ≤ 41) chronotype

You may not qualify if:

• Previously diagnosed with type 2 diabetes
• Moderate to severe anemia (hemoglobin \< 10 g/L)
• Uncontrolled hypertension
• Abnormal electrocardiogram (ECG) at rest judged by the study physician
• Pregnancy or breastfeeding
• HIV, hepatitis B, or C infection
• Disorders of blood clotting or wound healing
• Positive history of venous thrombosis (contraindication for clamp)
• Hypersensitivity to local anesthetics (contraindication for fat/muscle biopsies)
• Night shift work in the last 3 months
• Travel across \> 1 time zone in the last 3 months
• Participation in another clinical trials that may possibly hamper the study results
• Engagement in structured exercise activities \> 2 hours a week
• Any acute condition, exacerbation of chronic condition, or medical history that in the investigator's opinion would interfere with the study
• Any contraindication for MRI scanning

Sponsors & Collaborators

• German Diabetes Center: lead

Study Sites (1)

German Diabetes Center (DDZ)

Düsseldorf, 40225, Germany

Location

Related Publications (3)

• Keller MJ, Brady AJ, Smith JAB, Savikj M, MacGregor K, Jollet M, Oberg SB, Nylen C, Bjornholm M, Rickenlund A, Carlsson M, Caidahl K, Krook A, Pillon NJ, Zierath JR, Wallberg-Henriksson H. Inflammatory markers and blood glucose are higher after morning vs afternoon exercise in type 2 diabetes. Diabetologia. 2025 Sep;68(9):2023-2035. doi: 10.1007/s00125-025-06477-5. Epub 2025 Jun 28.

  PMID: 40580209 BACKGROUND

• Mancilla R, Brouwers B, Schrauwen-Hinderling VB, Hesselink MKC, Hoeks J, Schrauwen P. Exercise training elicits superior metabolic effects when performed in the afternoon compared to morning in metabolically compromised humans. Physiol Rep. 2021 Jan;8(24):e14669. doi: 10.14814/phy2.14669.

  PMID: 33356015 BACKGROUND

• Savikj M, Gabriel BM, Alm PS, Smith J, Caidahl K, Bjornholm M, Fritz T, Krook A, Zierath JR, Wallberg-Henriksson H. Afternoon exercise is more efficacious than morning exercise at improving blood glucose levels in individuals with type 2 diabetes: a randomised crossover trial. Diabetologia. 2019 Feb;62(2):233-237. doi: 10.1007/s00125-018-4767-z. Epub 2018 Nov 13.

  PMID: 30426166 BACKGROUND

MeSH Terms

Conditions

Prediabetic State; Overweight; Obesity; Motor Activity

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Study Officials

• Patrick Schrauwen, PhD

  German Diabetes Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrick Schrauwen, PhD

CONTACT

+49 211 3382-689; patrick.schrauwen@ddz.de

Friedrich C. Jassil, PhD

CONTACT

+49 211 3382-685; friedrich.jassil@ddz.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Participants will receive a code so that the person in charge with the data quality check and data analyses will be blinded to the interventions
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2026
• First Posted: February 5, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: February 5, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)