The Effect of Psilocybin on MDD Symptom Severity and Synaptic Density

NCT04630964 | Completed Phase 2

• 1 other identifier: 2020-002790-94
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

PROTOCOL SYNOPSIS Title The effect of psilocybin on Major depressive disorder (MDD) symptom severity and synaptic density - a single dose randomized, double blind, placebo-controlled phase 2b positron emission tomography study Study Code PSIPET Name of Sponsor SLSO Organisationsnr: 232100-0016 Sponsor representative: Andreas Carlborg Norra Stockholms Psykiatri Vårdvägen 3 112 19 Stockholm Sweden Medical Monitor Inspira Medical AB Phase of Study Phase 2b Sample Size 30 randomized Name of Investigational Product (IP) Psilocybin, 3-\[2-(dimethylamino)ethyl\]-1H-indol-4-yl\] dihydrogen phosphate Name of Active Placebo Niacin EudraCT 2020-002790-94 Description of IP and Active Placebo PSIPET Protocol 5 200821 Page 14 Study Intervention Name: Psilocybin (active drug product) Niacin (active placebo product) Dosage formulation: One active capsule contains 25 mg of psilocybin One active placebo capsule contains 100 mg of niacin Capsule: Size 2 hydroxypropyl methylcellulose (HPMC), opaque Size 2 HPMC, opaque Unit dose strength: 25 mg 100 mg Route of Administration: Oral (solid dose) Oral (solid dose) Dosing instructions: One capsule administered with water One capsule administered with water Packaging and Labeling: Study Intervention will be provided in a high-density polyethylene (HDPE) bottle. Each bottle will contain one capsule (psilocybin or niacin) and will be labeled as required per Swedish requirement for blinded study.

Conditions

Major Depressive Disorder; Depression

Outcome Measures

Primary Outcomes (1)

• Montgomery Åsberg Depression Rating Scale (MADRS)

  Change in blind rater MADRS total score. MADRS range: 0-60. Higher scores mean worse outcome.

  8 days

Secondary Outcomes (1)

• [11C]UCB-J

  7 to 1 day before dosing to 15 +/-7 days after dosing.

Study Arms (2)

psilocybin

EXPERIMENTAL

25 mg Single Oral Dose

Drug: Psilocybin

placebo

ACTIVE COMPARATOR

100 mg Single Oral Dose

Drug: Niacin

Interventions

Psilocybin DRUG

psilocybin 25 mg Single Oral Dose

psilocybin

Niacin DRUG

niacin 100mg Single Oral Dose

placebo

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals eligible to be randomized in this protocol are those who meet all of the following criteria:
• Are 20 to 65 years old at the time of written informed consent at the In-Person Screening visit
• Are able to read, speak, and understand Swedish
• Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations
• Are able to swallow capsules
• Women of childbearing potential (WOCBP) must agree to practice an effective means of birth control throughout the duration of the study, from Screening through the Day 42 assessment
• Meet ICD-10 criteria for a diagnosis of remitting major depressive disorder and are currently experiencing a major depressive episode of
• at least a 30-day duration at the time of the Screening
• less than 5 years at time of Screening
• Have sustained moderate-severe depression symptoms at Screening and Baseline, as defined by a Screening MADRS total score ≥ 22 and ≤30% and ≤7 point improvement (i.e. decrease) in MADRS total score from web-screening to screening visit (assuming 3 points on item 1 at web screening).
• \. Have an identified support person
• a. Agree to be driven/accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing

You may not qualify if:

• Individuals not eligible to be randomized in this protocol are those who meet any of the following criteria:
• Women who are pregnant, as indicated by a positive urine pregnancy test at Screening or Baseline. Women who intend to become pregnant during the study or who are currently nursing.
• Current depressive episode lasting \>5 years
• \. Unwilling or unable to discontinue formal psychotherapy 3. Ongoing antidepressant drug treatment 4. Have previously during the current episode received the following non-medication treatments:
• a. deep brain stimulation (DBS) b. vagus nerve stimulation (VNS) 5. Currently receiving electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) 6. Unable or unwilling to discontinue any current medications that are known uridine diphosphate (UDP) or glucuronosyltransferase (UGT) enzyme modulators (eg valproate)
• Note: Any prohibited agents must have been stopped at least 5x the elimination half-life of the specific drug at the time of Baseline. See Appendix A for a full list of prohibited medications.
• \. Report psychedelic substances use ever
• Note: Psychedelic substances include psilocybin, Lysergic acid diethylamide (LSD), mescaline (and natural products containing mescaline including peyote and San Pedro cactus), N,N-Dimethyltryptamine (DMT), natural products containing DMT including ayahuasca and 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), ibogaine, 2C compounds, 3,4-methylenedioxy- methamphetamine (MDMA), methylone or other psychedelics.
• \. Have the following cardiovascular conditions:
• a. coronary artery disease, congenital long QT syndrome (prior diagnosis), cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction (prior diagnosis); b. tachycardia (defined as heart rate \> 100 beats per minute); c. a clinically significant Screening ECG abnormality (e.g., atrial fibrillation); oNote: A QTcF interval \> 450 milliseconds is considered a clinically significant ECG abnormality d. artificial heart valve; or e. any other significant current or history of cardiovascular condition, based on the clinical judgment of study physician, that would make a participant unsuitable for the study 9. At Screening or Baseline have elevated blood pressure as defined as:
• a. Screening blood pressure SBP \>135 mmHg or DBP \> 85 mmHg on three separate readings; or b. Baseline blood pressure SBP \>140 mmHg or DBP \> 90 mmHg on three separate readings 10. Have a history of stroke or Transient Ischemic Attack (TIA) 11. Have moderate to severe hepatic impairment, as indexed by a Child-Pugh score ≥ 7 12. Have epilepsy 13. Have insulin-dependent diabetes
• Note: Participants who are taking oral hypoglycemic agent and have a history of hypoglycemia requiring medical intervention will be excluded 14. Are unable or unwilling to adhere to the following medication requirements:
• Agree to suspend sildenafil (Viagra®), tadalafil, or similar medications at least 72 hours prior to dosing
• If taking any supplement containing \>20 mg of niacin, agrees to suspend use for the duration of the study 15. Have a positive urine drug test including Amphetamines, Barbiturates, Buprenorphine, Benzodiazepines, Cocaine, Cannabis, Methamphetamine, MDMA, Methadone, Opiates (Morphine, Oxycodone), Phencyclidine (PCP), and Tetrahydrocannabinol (THC). Exceptions are made for prescribed Benzodiazepines (stable dose for sleep or anxiety).
• Note: Benzodiazepine medications for sleep and non-benzodiazepine sleeping medications will be allowed to continue through the study period for participants who have been on a stable dose of such a medicine for at least 6 weeks prior to Screening, as determined during review of concomitant medications

Sponsors & Collaborators

• Section for Affective Disorders; Northern Stockholm Psychiatry: lead
• Karolinska Institutet: collaborator

Study Sites (1)

Northern Stockholm Spychiatry Clinic

Stockholm, Sweden

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Psilocybin; Niacin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: November 16, 2020
• Study Start: January 1, 2021
• Primary Completion: April 19, 2023
• Study Completion: April 18, 2024
• Last Updated: April 19, 2024

Record last verified: 2024-04

Locations

SE (1)