Psilocybin for Depression in People With Mild Cognitive Impairment or Early Alzheimer's Disease

Sponsor

Johns Hopkins University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04123314

Collaborator

(none)

Enrollment

Location

Arm

33.2

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This open-label pilot study examines whether the hallucinogenic drug, psilocybin, given under supportive conditions, is safe and effective for depression in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD). This study will also assess whether psilocybin may improve quality of life in those individuals.

Condition or Disease	Intervention/Treatment	Phase
Depressive Symptoms Depression Alzheimer Disease Mild Cognitive Impairment	Drug: Psilocybin	Early Phase 1

Detailed Description

This is a pilot study evaluating the potential efficacy of psilocybin to produce improvement in depression compared to pre-treatment in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD) and clinically significant symptoms of depression. The study will be an open-label trial in a sample of up to 20 treatment-seeking participants with a diagnosis of MCI or early AD. Participants will complete an 8-week course of study treatment including two psilocybin sessions (15 mg/70 kg in week 4 and 15 or 25 mg/70 kg in week 6), with follow-up assessments up to 6 months after the final psilocybin session. The study will assess changes in depressed mood at 1 week after the second psilocybin session compared to pre-treatment, and quality of life in participants from pre- to post-treatment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pilot Study of Serotonin 2A Receptor (5-HT2A) Agonist Psilocybin for Depression in Patients With Mild Cognitive Impairment or Early Alzheimer's Disease

Actual Study Start Date :

Mar 24, 2021

Anticipated Primary Completion Date :

Dec 30, 2023

Anticipated Study Completion Date :

Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Psilocybin Participants will complete an 8-week course of study treatment including weekly psychological support and two moderate to high dose psilocybin administrations in weeks 4 and 6.	Drug: Psilocybin Dosing at the first session will be 15 mg/70 kg. For the second session participants will either remain at the initial dose, or increase to 25 mg/70 kg at the discretion of the study team.

Arm

Intervention/Treatment

Experimental: Psilocybin

Participants will complete an 8-week course of study treatment including weekly psychological support and two moderate to high dose psilocybin administrations in weeks 4 and 6.

Drug: Psilocybin

Dosing at the first session will be 15 mg/70 kg. For the second session participants will either remain at the initial dose, or increase to 25 mg/70 kg at the discretion of the study team.

Outcome Measures

Primary Outcome Measures

Change in Cornell Scale for Depression in Dementia (CSDD) score [Baseline and 1 week after second psilocybin session]
The Cornell Scale for Depression in Dementia (CSDD) is administered via patient and informant interviews to assess the presence and severity of depressive mood and behavioral symptoms during the past week. Has 19 items, each scored from 0 to 2 with higher scores indicating severe symptom.Total score range from 0 to 38.

Secondary Outcome Measures

Change in Quality of Life Alzheimer's Disease (QOL-AD) scale score [Baseline and 2 weeks after second psilocybin session]
The Quality of Life Alzheimer's Disease (QOL-AD) scale is a 13-item measure administered via patient and informant interviews to assess overall mood, physical and cognitive function, and quality of relationships in people with Alzheimer's Disease. Each item is scored 1 to 4, with higher score indicating better quality of life. Total score range from 13 to 52.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must meet either A) Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria for Mild Neurocognitive Disorder due to AD or Major Neurocognitive Disorder due to AD with Mild severity (including probable), or B) meet criteria for MCI including a subjective memory complaint relative to previous functioning and confirmed by Clinical Dementia Rating (CDR) Memory score at screening of >0.5
Have Mini-Mental State Examination scores from 18 to 26 (inclusive)
Have Cornell Scale for Depression in Dementia (CSDD) patient score > 6, indicating at minimum a mild to moderate degree of distress; or 2) a DSM-5 diagnosis of Major Depressive Disorder, Persistent Depressive Disorder, Mood Disorder due to a Medical Condition, or Adjustment Disorder with depressed mood or with mixed anxiety and depressed mood
Have a close friend or family member willing and able to serve the role of community observer / informant for data collection procedures

Exclusion Criteria:

Currently taking antidepressants of any drug class, antipsychotics, or Monoamine Oxidase (MAO) inhibitors
Participants must agree not to take sildenafil, tadalafil, or similar medications within 72 hours of each psilocybin administration, as these medications may potentiate hypotensive reactions to psilocybin
Cardiovascular conditions: angina, a clinically significant ECG abnormality (e.g. atrial fibrillation or QTc >450msec), Transient Ischemic Attack (TIA) in the last 6 months, stroke, artificial heart valves, or uncontrolled hypertension with resting blood pressure systolic >150 or diastolic >95
Minimum acceptable heartrate at screening is 50 bpm unless the individual is cleared for participation by a cardiologist, in accord with the American College of Cardiology's 2018 guidelines for bradycardia
Seizure disorder
Insulin dependent diabetes mellitus
Renal disease (creatinine clearance < 40 ml/min using the Cockcroft and Gault equation)
Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder
Family (i.e., 1st degree relative) history of Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder