Effects of Ghrelin Administration on Motivation
NCT Number: NCT06576440
Status: ENROLLING_BY_INVITATION
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Major Depressive Disorder
Interventions: DRUG: Ghrelin|DRUG: Saline
Sponsor: University Hospital Tuebingen
Sex: ALL
Age: ADULT
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: TRIPLE (PARTICIPANT, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: BASIC_SCIENCE
Start Date: 2024-09-02
Completion Date: 2025-01
Locations: Department of Psychiatry & Psychotherapy, University of Tübingen, Tübingen, BW, 72076, Germany

Summary:
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.

Primary Outcome Measures: 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)