The Effect of Psilocybin on Depressive Symptom Severity and Neuronal Connection Density – A Single Dose Randomized, Double Blind, Placebo-Controlled Phase 2 Positron Emission Tomography Study

Phase 1

• Conditions: Major Depressive Disorder; MedDRA version: 20.0Level: LLTClassification code 10025462Term: Major depressive disorder, recurrent episode, unspecified degreeSystem Organ Class: 100000004873; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2020-002790-94-SE
• Lead Sponsor: SLSO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-06-30
• Last Update Posted: 16 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Inclusion Criteria
Individuals eligible to be randomized in this protocol are those who meet all of the following criteria:

1. Are 20 to 65 years old at the time of written informed consent at the In-Person Screening visit
2. Are able to read, speak, and understand Swedish
3. Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations
4. Are able to swallow capsules
5. 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
6. Meet ICD-10 criteria for a diagnosis of remitting major depressive disorder and are currently experiencing a major depressive episode of
a) at least a 30-day duration at the time of the Screening
b) less than 5 years at time of Screening
7. 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).
9. 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria
Individuals not eligible to be randomized in this protocol are those who meet any of the following criteria:

1.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.
2.Current depressive episode lasting >5 years
2. 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)
o 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.
7. Report psychedelic substances use ever
o 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.
8. 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
o 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:
a. Agree to suspend sildenafil (Viagra®), tadalafil, or similar medications at least 72 hours prior to dosing
b. 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).
o Note: Benzodiazepine

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified