Physical Inactivity and Appetite Regulation

The Effects of Inactivity on GLP-1 Stimulated Appetite Regulation in Healthy Normal Weight Males: A Randomised, Parallel Group Study

The goal of this parallel-group, two-arm, assessor-blinded, randomised clinical trial is to investigate the effects of reducing physical activity on food intake and satiety in physically active and healthy males, 40-55 years of age.

The main questions it aims to answer are:

• Does physical inactivity affect GLP-1 stimulated food intake?
• Does physical inactivity affect food preferences, satiety and other mechanisms supporting appetite regulation?

Participants will be randomised (1:1) to two weeks of either no intervention (control group) or inactivity. Inactivity will be implemented as cessation of active commuting and all other structured exercise. Furthermore, steps will be reduced to a maximum of 1500 steps/day.

Researchers will compare the inactivity group to the control group to see if physical inactivity impairs appetite regulation.

Study Overview

• Status: Recruiting
• Conditions: Overweight
• Intervention / Treatment: Behavioral: Inactivity

Detailed Description

To contextualize the changes in ad libitum food intake driven by two weeks of physical inactivity, a sub-study will assess the effect of GLP-1 infusion on ad libitum food intake compared with a saline control in 20 participants included based on same eligibility criteria as in the main study. The estimated GLP-1 induced change in ad libitum food intake will be descriptively compared to the estimated GLP-1 + inactivity induced change in ad libitum food intake (main-study) to provide context for any attenuation in appetite suppression observed in the main-study. Outcomes related to subjective appetite measures (hunger, satiety, and food preference) will also be assessed in this way.

The primary hypothesis is that GLP-1 infusion will suppress appetite and reduce ad libitum food intake compared with saline control. The secondary hypothesis is that GLP-1 infusion will diminish subjective feelings of hunger and increase satiety.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Inge Holm; Phone Number: +45 35 45 76 41; Email: inge.holm@regionh.dk
• Study Contact Backup: Name: Bente K Pedersen, Dr Med; Phone Number: +45 35 45 76 41; Email: Bente.Klarlund.Pedersen@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Copenhagen University Hospital
    • Contact: Grit E Legård; Phone Number: +45 35457641; Email: grit.elster.legaard@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male
2. Age ≥ 40 years and ≤ 55 years
3. Body mass index (BMI) > 20 and < 25 kg/m2
4. Physical activity level should as a minimum include: Active commuting by biking a minimum of 10 km, four days per week or an equivalent amount of other physical activity four days per week.
5. Healthy (based on self-reporting, pre-study medical examination and biochemical screening)
6. Can adhere to two weeks of inactivity (refrain from running, cycling and all other exercise while reducing steps to max. 1500 pr. day)
7. Caucasian
8. No change in body weight > 5 kg within the last 6 months
9. Eats breakfast and lunch daily
10. Does not follow specific dietary restrictions
11. No disliking of spaghetti bolognese
12. No diagnosis of psychiatric disorder or treatment with anti-depressant or anti-psychotic medication
13. No history of suicidal behavior or ideations.
14. No previous surgical treatment for obesity
15. No cardiovascular disease
16. No rheumatologic disease
17. No metabolic/endocrine disease
18. No liver disease (ASAT or ALAT >2x upper normal range)
19. No other chronic disease
20. No elite sports
21. No frequent or chronic use of medications affecting bodyweight, physical performance, or inflammation (NSAIDS, DMARDS, corticosteroids)
22. No current infection
23. No history of cancer
24. No anemia (hematocrit <33%)
25. No smoking
26. No participation in other research intervention studies

Exclusion Criteria:

1. Clinical or biochemical signs of disease
2. HbA1c > 39 mmol/mol
3. Unable to allocate the needed time to fulfill the intervention
4. Language barrier, mental incapacity, unwillingness, or inability to understand and be able to complete the interventions

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: Inactivity; Inactivity will be implemented as cessation of active commuting and all other structured exercise. Furthermore, steps will be reduced to a maximum of 1500 steps/day.	Behavioral: Inactivity; Inactivity will be implemented as cessation of active commuting and all other structured exercise. Furthermore, steps will be reduced to a maximum of 1500 steps/day.
No Intervention: Control; Participants will be instructed to maintain habitual physical activity and dietary habits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in food intake at an ad libitum meal during GLP-1 infusion	Food intake will be evaluated as ingested food in grams	From baseline (week 0) to follow-up (week 2).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in preference for unhealthy food ( combined score for high fat food, savory food, and sweet food).	Evaluated by visual food stimuli combined with eye tracking	From baseline (week 0) to follow-up (week 2)
The change in subjective experience of severity and type of food cravings	Evaluated by the Control of Eating Questionnaire.	From baseline (week 0) to follow-up (week 2)
The change in subjective feeling of satiety	Evaluated by a visual analogue scale	From baseline (week 0) to follow-up (week 2)
The change in subjective felling of hunger	Evaluated by a visual analogue scale	From baseline (week 0) to follow-up (week 2)
The change in satiety composite appetite score	Calculated from visual analog scales	From baseline (week 0) to follow-up (week 2)
Sub study	Comparison between Ad libitum meal +/- GLP-1 infusion on primary and secondary outcomes of the primary study.	Sub study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in secretion of gut hormones (GLP-1, GIP, PYY, ghrelin, CCK)		From baseline (week 0) to follow-up (week 2)
Change in gastric emptying rate	Measured by surrogate marker paracetamol	From baseline (week 0) to follow-up (week 2)
Change in body composition (body weight, body mass index, lean mass, fat mass)	Based on DXA scans	From baseline (week 0) to follow-up (week 2)
Change in physical fitness (maximal aerobic capacity, one repetition max)		From baseline (week 0) to follow-up (week 2)
Change in plasma glucose during ad libitum meal	AUC (mol/hour)	From baseline (week 0) to follow-up (week 2)
Change in plasma insulin during ad libitum meal	AUC (mol/h)	From baseline (week 0) to follow-up (week 2)
Change in plasma c-peptide during ad libitum meal	AUC (mol/hour)	From baseline (week 0) to follow-up (week 2)
Change in glucagon supression during ad libitum meal	The % glucagon supression at time 0-30min, 0-60min and 0-120min	From baseline (week 0) to follow-up (week 2)
Change in plasma insulin/glucagon ratio during ad libitum meal	Insulin/glucagon at time=30, 60 and 120	From baseline (week 0) to follow-up (week 2)
Change in plasma glucose during mixed meal tolerance test	AUC (mol/hour)	From baseline (week 0) to follow-up (week 2)
Change in plasma insulin during mixed meal tolerance test	AUC (mol/hour)	From baseline (week 0) to follow-up (week 2)
Change in insulin/c-peptide ratio during mixed meal tolerance test	Insulin/glucagon at time 30min, 60min, 120min and 180	From baseline (week 0) to follow-up (week 2)
Change in plasma c-peptide during mixed meal tolerance test	AUC (mol/hour)	From baseline (week 0) to follow-up (week 2)
Change in glucagon supression during mixed meal tolerance test	The % glucagon supression at time 0-30min, 0-60min, 0-120min and 0-180	From baseline (week 0) to follow-up (week 2)
Change in plasma insulin/glucagon ratio during mixed meal tolerance test	Insulin/glucagon at time 30min, 60min, 120min and 180	From baseline (week 0) to follow-up (week 2)
Change in plasma concentration of cytokines (IL-1Ra, IL-6, IL-10, CRP, TNF-α, GDF-15)		From baseline (week 0) to follow-up (week 2)
Change in plasma concentration of adipokines (leptin and adiponectin)		From baseline (week 0) to follow-up (week 2)
Change in glycaemic variability	CV% derived from free-living continuous glucose monitoring	From baseline (week 0) to follow-up (week 2)
Change in glycaemic variability	SD derived from free-living continuous glucose monitoring	From baseline (week 0) to follow-up (week 2)
Change in glycaemic variability	Mean glucose derived from free-living continuous glucose monitoring	From baseline (week 0) to follow-up (week 2)
Change in glycaemic variability	Time in range derived from free-living continuous glucose monitoring	From baseline (week 0) to follow-up (week 2)
Change in physical and mental well-being	Based on scores from WHO5, HAM-DS-S, and GAD-10 questionnaires	From baseline (week 0) to follow-up (week 2)
Change in physical and mental well-being	Based on scores from WHO5 questionnaires	From baseline (week 0) to follow-up (week 2)
Change in symptoms of depression	Based on scores from HAM-D6-S questionnaires	From baseline (week 0) to follow-up (week 2)
Change in symptoms of anxiety	Based on scores from GAD-10 questionnaires	From baseline (week 0) to follow-up (week 2)
Change in sleep Quality	Based on scores from Pittsburgh Sleep Quality Index	From baseline (week 0) to follow-up (week 2)
Change in plasma peptides	Evaluated by peptidomics	From baseline (week 0) to follow-up (week 2)
Change in plasma metabolites	Evaluated by metabolomics	From baseline (week 0) to follow-up (week 2)

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Novo Nordisk A/S; TrygFonden, Denmark
• Investigators: Principal Investigator: Grit Elster Legård, MD, PhD, Centre for Physical Activity Research, Rigshospitalet

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 17, 2024
• First Submitted That Met QC Criteria: January 26, 2024
• First Posted (Actual): February 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight
• Other Study ID Numbers: H-23055497

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: If the data can be fully anonymized the data can be shared

Drug and device information, study documents

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