Psilocybin and Depression (Psilo101)

• ClinicalTrials.gov Identifier: NCT03380442
• Recruitment Status: Unknown
• First Posted: December 21, 2017
• Last Update Posted: December 21, 2017
• Sponsor: University of Helsinki
• Collaborators: Dr. Tomi Rantamäki, Laboratory of Neurotherapeutics, Department of Biosciences, University of Helsinki; Dr. Robin Carthart-Harris and Prof. David Nutt, Imperial College London, UK
• Information provided by (Responsible Party): Jesper Ekelund, University of Helsinki

Study Description

Brief Summary:

The main aim of the study is to investigate the possible long-term therapeutic effects of psilocybin on the symptoms of severe depression, as well as the brain mechanisms underlying these changes. Depression severity is assessed before and after (i.e., 1 week, 3 months and 6 months after) a single dose of psilocybin and compared to respective scores of a group receiving an active placebo, ketamine. Brain activity (using functional magnetic resonance imaging) is measured before and one week after drug administration in order to determine whether changes in brain networks related to emotional and self-referential processing correlate with any observed changes in depression scores. Further, blood samples will be obtained from the participants and analyzed in order to reveal gene expression and molecular level correlates underlying rapid antidepressant effects, and to identify biomarkers that predict treatment outcome.

Condition or disease	Intervention/treatment	Phase
Severe Depression	Drug: Psilocybin; Drug: Ketamine (Ketalar)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: In a randomized, double-blind placebo-controlled design, 20 of the participants will receive ketamine, and 20 will receive psilocybin. 20 of the participants will be included in the study as a no-treatment group, so that natural time-dependent changes in depressive symptoms can be controlled for and thus the antidepressive effects of ketamine and psilocybin treatment can be verified. The no-treatment group will only attend the initial clinical interviews, and their depressive symptoms will be assessed remotely.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Since the psilocybin is ingested orally in capsule form, whereas ketamine is administered intranasally, the participants will either receive a placebo capsule containing microcrystalline cellulose (if they belong to the group receiving ketamine), or intranasally administered saline solution (with added bitter flavoring which will mimic the taste of ketamine that is often detectable even when administered intranasally).
• Primary Purpose: Basic Science
• Official Title: Psilocybin and Depression - Assessing the Long-term Effects of a Single Administration of Psilocybin on the Psychiatric Symptoms and Brain Activity of Patients With Severe Depression
• Estimated Study Start Date: September 2018
• Estimated Primary Completion Date: January 2020
• Estimated Study Completion Date: September 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Psilocybin group; This group will receive a single oral 25mg dose of psilocybin under surveilled and safe conditions.	Drug: Psilocybin; Psilocybin ingested orally
Active Comparator: Ketamine group; This group will receive a single intranasal 125mg dose of ketamine under surveilled and safe conditions.	Drug: Ketamine (Ketalar); Ketamine administered intranasally
No Intervention: No-treatment group; This group will be included in the study as a no-treatment group, so that natural time-dependent changes in depressive symptoms can be controlled for and thus the antidepressive effects of ketamine and psilocybin treatment can be verified

Outcome Measures

Primary Outcome Measures :

1. The 16-Item Quick Inventory of Depressive Symptomatology (QIDS) [ Time Frame: 6 months ]
   The primary outcome measures in this study will be the mean change in QIDS scores from pre-administration baseline at day 1 to Follow-up 2 at day 103 (3 months after the administration session). Additionally, an electronic version of the QIDS will be performed 6 months after the administration session. The criteria for determining response will be a reduction of 25% in the (QIDS; Rush et al., 2003) scores from baseline (screening), and remission will be scores of ≤5 on the QIDS.

Secondary Outcome Measures :

1. The Montgomery and Asberg Depression Rating Scale [ Time Frame: 3 months ]
   The Montgomery and Asberg Depression Rating Scale will be carried out at screening ( day 1), Follow-up 1 (day 18) and Follow-up 2 (day 103, 3 months after the administration session).
2. Hamilton Depression Rating Scale [ Time Frame: 3 months ]
   The Hamilton Depression Rating Scale will be carried out at screening ( day 1), Follow-up 1 (day 18) and Follow-up 2 (day 103, 3 months after the administration session).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Major depression of a moderate to severe degree (17+ on the 21-item HAM-D).
2. No health-related contraindications.

Exclusion Criteria:

1. Current or previously diagnosed psychotic disorder.
2. Immediate family member with a diagnosed psychotic disorder.
3. Medically significant condition rendering unsuitability for the study (e.g., diabetes, epilepsy, severe cardiovascular disease, hepatic or renal failure etc.).
4. History of suicide attempts.
5. History of mania.
6. Current 5-HT2A antagonist antidepressant medication.
7. Blood or needle phobia.
8. Positive pregnancy test.
9. Current drug or alcohol dependence.
10. Lack of appropriate use of contraception.
11. Breast-feeding.

Contacts and Locations

Contacts

Contact: Mona E Moisala, PhD; 504480044 ext +358; mona.moisala@helsinki.fi

Sponsors and Collaborators

University of Helsinki

Dr. Tomi Rantamäki, Laboratory of Neurotherapeutics, Department of Biosciences, University of Helsinki

Dr. Robin Carthart-Harris and Prof. David Nutt, Imperial College London, UK

More Information

• Responsible Party: Jesper Ekelund, Professor of Psychiatry, University of Helsinki
• ClinicalTrials.gov Identifier: NCT03380442
• Other Study ID Numbers: 2016-004195-22
• First Posted: December 21, 2017
• Last Update Posted: December 21, 2017
• Last Verified: December 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jesper Ekelund, University of Helsinki:

fMRI; psilocybin; ketamine; biomarker; rapid-acting antidepressants

Additional relevant MeSH terms:

Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders; Ketamine; Psilocybin; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hallucinogens; Psychotropic Drugs