Major Depressive DisorderPhase 1/2NCT05318924
Effects of Ghrelin Administration on Dopamine and Effort
A Phase 1/2 study testing Ghrelin in people with Major Depressive Disorder, run by University Hospital Tuebingen at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 20 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Ghrelin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteGermany
- Study dates
- 21 Feb 2022to 6 Aug 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Psychiatry & Psychotherapy, University of Tübingen
Tübingen, Baden-Wurttemberg, 72076
About this study
Official title: Will Work for Reward: Effects of Ghrelin Administration on Dopamine and Effort
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.
- Conditions
- Major Depressive Disorder
- Being tested
- Ghrelin, Placebo
- Keywords
- energy homeostasis, PET/MR, dopamine, motivation, ghrelin
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GhrelinDrug
Participants will receive an infusion that is intended to raise ghrelin level up to a steady plateau.
PlaceboOther
Participants will receive a saline infusion as the placebo control condition.
| Study group | Role | What they receive |
|---|---|---|
| Ghrelin infusion | Experimental | To achieve approximately stable elevated ghrelin levels during the infusion procedure, the investigators will use a loading dose of 1 mcg/kg as well as an infusion rate of 0.051 mcg/kg/min in line with recent studies (Farokhnia, Grodin, Lee et al., 2017) and general recommendations (Garin, Burns, Kaul et al., 2013). Receives: Drug: Ghrelin |
| Placebo infusion | Placebo comparator | Saline Receives: Other: Placebo |
| Patients with MDD | No intervention | Patients with major depressive disorder will be enrolled for comparison to healthy participants on the reward task battery, but not randomized to the ghrelin vs. saline infusion. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ghrelin-induced changes in dopamine release
[11C]raclopride binding potential after ghrelin infusion vs. saline infusion
Measured: During the infusion (up to 90 min)
Ghrelin-induced changes in motivation
Force exerted on grip force controller to obtain rewards after ghrelin infusion vs. saline infusion
Measured: During the infusion (60-90 min after start of the infusion)
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
Measured: During the infusion (up to 90 min)
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
Measured: Pre infusion and 20 minutes post infusion (compared to saline)
Secondary outcomes (1)
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
Measured: Pre infusion and 20 minutes post infusion (compared to saline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2022
- Study start21 Feb 2022
- Primary completion6 Aug 2024
- Study completion6 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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, 26 healthy 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). These 26 healthy participants will be drawn from a larger sample of 100 participants (including 50 patients with major depressive disorders), who will complete a reward task battery that will be associated with fasting blood levels of ghrelin.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- German Research Foundation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05318924
- Sponsor's protocol ID
- DFG KR 4555/7-1
- Status last verified
- Dec 2025
- First submitted
- 22 Feb 2022
- Last updated
- 22 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After the publication of the key results of the study, all anonymized imaging data will be made publicly available (e.g., at openfmri.org). Behavioral data will be shared after aggregation at the trial or participant level.
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Will Work for Reward: Effects of Ghrelin Administration on Dopamine and Effort
- ClinicalTrials.gov ID
- NCT05318924
- Acronym / sponsor ID
- DFG KR 4555/7-1
- Conditions
- Major Depressive Disorder
- Keywords
- energy homeostasis, PET/MR, dopamine, motivation, ghrelin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Collaborators
- German Research Foundation
- Study start
- 21 Feb 2022 (actual)
- Primary completion
- 6 Aug 2024 (actual)
- Study completion
- 6 Aug 2024 (actual)
- First posted
- 8 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- 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, 26 healthy 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). These 26 healthy participants will be drawn from a larger sample of 100 participants (including 50 patients with major depressive disorders), who will complete a reward task battery that will be associated with fasting blood levels of ghrelin.
| Arm | Type | Receives |
|---|---|---|
| Ghrelin infusion | Experimental | Drug: GhrelinTo achieve approximately stable elevated ghrelin levels during the infusion procedure, the investigators will use a loading dose of 1 mcg/kg as well as an infusion rate of 0.051 mcg/kg/min in line with recent studies (Farokhnia, Grodin, Lee et al., 2017) and general recommendations (Garin, Burns, Kaul et al., 2013). |
| Placebo infusion | Placebo comparator | Other: PlaceboSaline |
| Patients with MDD | No intervention | –Patients with major depressive disorder will be enrolled for comparison to healthy participants on the reward task battery, but not randomized to the ghrelin vs. saline infusion. |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (3 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GhrelinParticipants will receive an infusion that is intended to raise ghrelin level up to a steady plateau. | Drug | Ghrelin infusion |
| PlaceboParticipants will receive a saline infusion as the placebo control condition. | Other | Placebo infusion |
Primary outcome
Ghrelin-induced changes in dopamine release
Time frame: During the infusion (up to 90 min)
[11C]raclopride binding potential after ghrelin infusion vs. saline infusion
Ghrelin-induced changes in motivation
Time frame: During the infusion (60-90 min after start of the infusion)
Force exerted on grip force controller to obtain rewards after ghrelin infusion vs. saline infusion
Ghrelin-induced changes in functional connectivity and perfusion
Time frame: During the infusion (up to 90 min)
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
Changes (Ghrelin-induced) in hunger and satiety from baseline
Time frame: Pre infusion and 20 minutes post infusion (compared to saline)
Change in visual analogue scale (0-100) measures of subjective hunger and satiety after ghrelin infusion vs. saline infusion
1 secondary outcome
Ghrelin-induced changes in mood
Time frame: Pre infusion and 20 minutes post infusion (compared to saline)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2025.
- Individual participant dataSharing planned: Yes. After the publication of the key results of the study, all anonymized imaging data will be made publicly available (e.g., at openfmri.org). Behavioral data will be shared after aggregation at the trial or participant level.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ghrelin in people with Major Depressive Disorder, run by University Hospital Tuebingen at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ghrelin-induced changes in dopamine release (time frame: During the infusion (up to 90 min)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2025.