An interventional study of Citalopram and Pindolol and Placebo in Healthy, sponsored by Gitte Moos Knudsen. Completed at 1 site in Denmark. Open to participants aged 18 Years to 100 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-02-20.
Sponsored by Gitte Moos Knudsen · Not applicable, Interventional, and Basic science
The purpose of this project was to introduce the recently developed positron emission tomography (PET) tracer [11C]Cimbi-36 for use in clinical studies and to investigate the ability of the tracer to quantify the 5-HT2A receptor in the human brain. As a receptor agonist, [11C]Cimbi-36 binding will provide a more functional picture of 5-HT2A receptors, while this binding is thought to be correlated to brain serotonin levels. Both measurement of signaling through the 5-HT2A receptor and measurement of serotonin levels in vivo would have great scientific relevance for significant diseases such as depression and schizophrenia.
The serotonin 2A (5-HT2A) receptor is the most abundant excitatory serotonin (5-HT, 5-hydroxytryptamine) receptor in the human brain, and multiple positron emission tomography (PET) studies have investigated the 5-HT2A receptors in the human brain using antagonist radioligands. However, the currently available antagonist PET radioligands bind the total pool of 5-HT2A receptor receptors whereas a 5-HT2A receptor agonist binds the high-affinity subgroup of the receptors which are also G-protein coupled, and thus hypothesized to be the functional relevant population of receptors. At the Center for Integrated Molecular Brain Imaging (CIMBI), a novel agonist PET radioligands for brain imaging of 5-HT2A receptors was recently validated in animals (Ettrup et al. 2011, EJNMMI). In the human brain, [11C]Cimbi-36 was validated as a selective 5-HT2A receptor agonist PET radioligand through a blocking study with the 5-HT2A receptor antagonist pharmaceutical ketanserin. In this validation study, the biodistribution and kinetic modelling of [11C]Cimbi-36 binding in the human brain was also validated. With these studies, investigators will test the most promising of these, [11C]Cimbi-36, in clinical trials, where it will provide a novel method for detecting dysfunction in the 5-HT system. The specific aim of this clinical trial is:
It is hypothesized that this novel agonist radioligand will provide both a more physiological relevant measure of the 5-HT2A receptors and also reflect levels of cerebral 5-HT in humans, more specifically:
BP will decrease after pindolol and selective serotonin reuptake inhibitor (SSRI) treatment and increase after acute tryptophan depletion (ATD). Placebo will leave binding potential (BP) unchanged.
Gitte Moos Knudsen is the lead sponsor of 8 studies on the registry; 2 are open to participants now.
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Citalopram intravenous infusion starting 30 min before scanning, 40 mg/h for 1 hour. Pindolol peroral administration starting 3 days before scanning: Day 1: 2.5 mg 3 times daily, day 2: 5 mg 3 times daily, day 3: 7.5 mg 3 times daily, Day 4 (scan day) 7.5 mg morning and noon.
Drug: Citalopram and Pindolol
Placebo for pindolol: sugar tablets that resembles pindolol Placebo for ATD: amino acid drink balanced formula (containing tryptophan) Placebo for Seropram: NaCl infusion
Other: Placebo
Amino acid drink without tryptophan. Ingested 4-5 hours prior to PET scanning.
Dietary Supplement: Acute tryptophan depletion
Drug pages: Citalopram · Pindolol
Citalopram: selective serotonin reuptake inhibitor Pindolol: non-selective beta blocker and 5-HT1A receptor antagonist
Also known as: Seropram, Hexapindol®
On the second PET scanning day, subjects received a protein drink as well as a 50 ml saline infusion over 1 hour starting 30 min before PET scanning.
Also known as: Amino acid drink without tryptophan
Percent Change in Neocortical [11C]Cimbi-36 BPND From Baseline to Intervention in Each Arm
Cerebral Cimbi-36 receptor binding is measured with PET scanning for 2 hours, at baseline and after intervention. The resultant time-activity curves for brain tissue are used together with time-activity curves obtained with blood samples and kinetic modelling to yield unitless values of BPND at baseline and after intervention, respectively. As outcome, the mean percent difference from baseline to intervention in each arm is measured.
Time frame: 2 hours
| Milestone | Citalopram and Pindolol | Placebo | Acute Tryptophan Depletion |
|---|---|---|---|
| Started | 8 | 8 | 8 |
| Completed | 8 | 8 | 7 |
| Not completed | 0 | 0 | 1 |
| Withdrew: Adverse event | 0 | 0 | 1 |
Cerebral Cimbi-36 receptor binding is measured with PET scanning for 2 hours, at baseline and after intervention. The resultant time-activity curves for brain tissue are used together with time-activity curves obtained with blood samples and kinetic modelling to yield unitless values of BPND at baseline and after intervention, respectively. As outcome, the mean percent difference from baseline to intervention in each arm is measured.
| percent change | Citalopram and Pindolol | Placebo | Acute Tryptophan Depletion |
|---|---|---|---|
| Percent Change in Neocortical [11C]Cimbi-36 BPND From Baseline to Intervention in Each Arm | 7.4 ± 16 | 0.6 ± 7.2 | 3.8 ± 0.2 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Citalopram and Pindolol | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) |
| Placebo | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) |
| Acute Tryptophan Depletion | 0/8 (0%) | 0/8 (0%) | 1/8 (12.5%) |
| Event | Citalopram and Pindolol | Placebo | Acute Tryptophan Depletion |
|---|---|---|---|
| AEGeneral disorders | 0/8 | 0/8 | 1/8 |
| Age, Categorical(Participants) | Citalopram and Pindolol | Placebo | Acute Tryptophan Depletion | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 8 | 8 | 8 | 24 |
| >=65 years | 0 | 0 | 0 | 0 |
| Age, Continuous(years) | Citalopram and Pindolol | Placebo | Acute Tryptophan Depletion | Total |
|---|---|---|---|---|
| Mean | 22.4 ± 2.1 | 22.6 ± 2.5 | 22.9 ± 3.2 | 22.6 ± 2.6 |
| Sex: Female, Male(Participants) | Citalopram and Pindolol | Placebo | Acute Tryptophan Depletion | Total |
|---|---|---|---|---|
| Female | 4 | 4 | 4 | 12 |
| Male | 4 | 4 | 4 | 12 |
| Region of Enrollment(participants) | Citalopram and Pindolol | Placebo | Acute Tryptophan Depletion | Total |
|---|---|---|---|---|
| Denmark | 8 | 8 | 8 | 24 |
This study is completed, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Citalopram · Pindolol
Gitte Moos Knudsen