Effects of Ghrelin Administration on Motivation

The Effects of Ghrelin Administration on Motivation and Resting Energy Expenditure

Everyday humans are confronted with a plethora of rewards competing for their attention. Nevertheless, to obtain a goal or reward, humans often need to invest effort. When humans are confronted with the challenge to integrate costs of action such as the effort of walking to one's favorite lunch place with its anticipated benefits (i.e., eating one's favorite meal), accumulating evidence suggest that humans might "go with the gut". Ghrelin is a stomach-derived hormone and the only known circulating peptide that stimulates appetite. At the same time, patients with major depressive disorder report deficits in motivated behavior which are oftentimes accompanied by changes in appetite and weight. Based on a wealth of accruing evidence from animal studies, the investigators suggest that the gut acts as an important arbitrator in effort allocation by signaling the energy level of the body. Within this physiological framework, ghrelin is thought to signal a short-term energy deficit to increase reward responsivity and willingness to work for reward as compensatory (allostatic) means. Here, the investigators propose to conduct a follow-up study (to NCT05318924) with subcutaneous administration of ghrelin vs. saline in patients with major depressive disorder and healthy control participants. During each visit, participants will receive a subcutaneous administration of either ghrelin or saline and perform an effort allocation task where they have to exert physical effort to obtain food and monetary rewards. The investigators hypothesize that ghrelin will increase the motivation to exert effort for rewards. The goal of this follow-up study is to test that the motivational effects of ghrelin are similar in patients with depression and healthy control participants. Furthermore, participants resting energy expenditure will be estimated before and after the administration. In line with a role of ghrelin as an energy deficit signal, the investigators expect ghrelin to decrease energy expenditure. During each visit, participants will answer questions about their current mood and physiological state. The investigators hypothesize that ghrelin increases mood state and hunger while decreasing satiety.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Ghrelin; Drug: Saline

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Baden-Wurttemberg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Department of Psychiatry & Psychotherapy, University of Tübingen

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

* Must have participated in the behavioral study arm of NCT05120336

Exclusion Criteria:

• participation in the neuroimaging part of NCT05120336
• breastfeeding
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Major depressive disorder; Patients with major depressive disorder will receive a subcutaneous injection of ghrelin (experimental) on one day and saline (placebo) on another day (order randomised; double-blind cross-over design).	Drug: Ghrelin; Participants in this arm will receive a subcutaneous injection of acyl-ghrelin as the active condition.; Other Names: Acyl-ghrelin; Drug: Saline; Participants in this arm will receive a subcutaneous injection of saline as placebo control condition.; Other Names: Placebo
Experimental: Healthy control participants; Healthy control participants will receive a subcutaneous injection of ghrelin (experimental) on one day and saline (placebo) on another day (order randomised; double-blind cross-over design).	Drug: Ghrelin; Participants in this arm will receive a subcutaneous injection of acyl-ghrelin as the active condition.; Other Names: Acyl-ghrelin; Drug: Saline; Participants in this arm will receive a subcutaneous injection of saline as placebo control condition.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ghrelin-induced changes in motivation	Frequency of button presses on a XBox controller to obtain rewards after ghrelin administration vs. saline administration	15-50 minutes after subcutaneous administration (ghrelin vs. saline)
Ghrelin-induced changes in Resting Energy Expenditure	Changes in energy expenditure after a ghrelin administration (vs. saline) as measured with indirect Calorimetry.	Pre injection versus 50-65 minutes after injection (compared to saline)
Ghrelin-induced changes in mood	Changes operationalized via visual analogue ratings (0-100) of the sum score of positive and negative affect schedule mood items after ghrelin administration vs. saline administration. Measures are taken ~40 minutes and 5 minutes prior to injection, as well as 15, 50, and 65 minutes after injection.	Pre injection timepoints (mean over 40 minutes and 5 minutes before) versus post injection timepoints (mean over 15, 50 and 65 minutes after injection) (compared to saline)
Ghrelin-induced changes in hunger and satiety from baseline	Change in visual analogue scale (0-100) measures of subjective hunger and satiety after ghrelin administration vs. saline administration. Measures are taken ~40 minutes and 5 minutes prior to injection, as well as 15, 50, and 65 minutes after injection.	Pre injection timepoints (mean over 40 minutes and 5 minutes before) versus post injection timepoints (mean over 15, 50 and 65 minutes after injection) (compared to saline)

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Nils B Kroemer, PhD, University of Tübingen, Faculty of Medicine, Department of Psychiatry & Psychotherapy

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2024
• Primary Completion (Actual): December 20, 2024
• Study Completion (Actual): December 20, 2024

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 28, 2024

Study Record Updates

• Last Update Posted (Actual): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: motivation; mood; ghrelin; anhedonia; energy homeostasis
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Mood Disorders; Depressive Disorder; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Depressive Disorder, Major; Anhedonia; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Sodium Chloride; Ghrelin; acyl-ghrelin
• Other Study ID Numbers: TUE008_ADMIN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After the publication of the key results of the study, behavioral data will be shared after aggregation at the trial or participant level.
• IPD Sharing Access Criteria: Until the data is publicly available, researchers may contact the lead PI to gain access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

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