Effects of Ghrelin Administration on Dopamine and Effort

Major Depressive Disorder Clinical Trial

Official title:

Will Work for Reward: Effects of Ghrelin Administration on Dopamine and Effort

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05318924
• Other study ID #: DFG KR 4555/7-1
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 21, 2022
• Est. completion date: October 31, 2024

Study information

• Verified date: February 2022
• Source: University Hospital Tuebingen
• Contact: Nils B Kroemer, PhD
• Phone: +4970712982021
• Email: nils.kroemer[@]uni-tuebingen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ghrelin is a stomach-derived hormone and the only known circulating peptide that stimulates appetite. Animal studies have conclusively shown that ghrelin increases dopaminergic neurotransmission and, thereby, enhances effort. However, similar evidence on the putative role of ghrelin in humans is still lacking. Here, the investigators propose to conduct a [11C]-raclopride PET/MR study after intravenous administration of ghrelin vs. saline in healthy individuals. First, during an intake visit, the investigators will assess fasting blood levels of hormones involved in appetitive behavior such as ghrelin, leptin, and insulin. In addition, the investigators will conduct a set of tasks that have been associated with dopamine function (i.e., effort and reinforcement learning). Second, the investigators will assess the effects of intravenous administration of ghrelin on dopamine signaling using a double-blind randomized cross-over design. To this end, participants will be infused with ghrelin (vs. saline) while we determine dopamine release (via PET imaging) and assess cerebral blood flow and functional connectivity at rest (via concurrent MR imaging). Furthermore, the investigators will conduct an instrumental motivation task (IMT) where participants have to exert physical effort to obtain rewards. Based on preclinical studies and indirect evidence from human studies, the investigators hypothesize that ghrelin will increase dopamine release in the striatum and that this will, in turn, lead to an increase in the willingness to work for rewards. Moreover, the investigators expect that ghrelin-induced dopamine release will be associated with an elevated tracking of reward utility in the mesolimbic circuit during the IMT, which is known to be associated with response vigor. Collectively, the proposed project would provide a unique resource to test an important link between the gut and the brain in the regulation of appetitive behavior. If ghrelin were to enhance effort expenditure for rewards via dopamine signaling in humans, then restoring sensitivity to ghrelin might be the more promising therapeutic approach compared to antagonizing the ghrelin receptor.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 31, 2024
• Est. primary completion date: December 20, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 50 Years

Eligibility

Inclusion Criteria:

• Healthy control participants: never fulfilled the criteria of any mood or anxiety disorder (except specific phobia)
• Patients with major depressive disorder: diagnosis according to DSM-5 within 12 months before enrollment and presence of at least mild symptoms at enrollment (BDI II >= 14)

Exclusion Criteria:

• lifetime history of a brain injury, schizophrenia, bipolar disorder, and a severe substance use disorder according to DSM-5
• obsessive-compulsive disorder, trauma- and stressor-related disorder, somatic symptom disorder, and eating disorder within a 12-month interval before the test day.
• Neuroimaging Study involving ghrelin infusion: contraindication for PET/MR (e.g., metal implants or prostheses, pregnancy, claustrophobia)

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Ghrelin
Participants will receive an infusion that is intended to raise ghrelin level up to a steady plateau.

Other:
• Placebo
Participants will receive a saline infusion as the placebo control condition.

Locations

Country	Name	City	State
Germany	Department of Psychiatry & Psychotherapy, University of Tübingen	Tübingen	BW

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Tuebingen	German Research Foundation

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ghrelin-induced changes in dopamine release	[11C]raclopride binding potential after ghrelin infusion vs. saline infusion	During the infusion (up to 90 min)
Primary	Ghrelin-induced changes in motivation	Force exerted on grip force controller to obtain rewards after ghrelin infusion vs. saline infusion	During the infusion (60-90 min after start of the infusion)
Primary	Ghrelin-induced changes in functional connectivity and perfusion	Functional connectivity and perfusion of regions of the reward circuit (i.e., Nucleus Accumbens and Ventral Tegmental Area/Substantia Nigra) after ghrelin infusion vs. saline infusion	During the infusion (up to 90 min)
Primary	Changes (Ghrelin-induced) in hunger and satiety from baseline	Change in visual analogue scale (0-100) measures of subjective hunger and satiety after ghrelin infusion vs. saline infusion	Pre infusion and 20 minutes post infusion (compared to saline)
Secondary	Ghrelin-induced changes in mood	Changes operationalized via visual analogue ratings (0-100) of positive and negative affect schedule mood items after ghrelin infusion vs. saline infusion	Pre infusion and 20 minutes post infusion (compared to saline)