Clinical trial NCT06656702: Effects of Psilocybin in Patients With Amyotrophic Lateral Sclerosis
Official title: Effects of Psilocybin in Patients With Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2024-10-24
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to study the feasibility of psilocybin therapy for patients with Amyotropic Lateral Sclerosis (ALS) with depressed mood. The secondary objective is to assess its impact on depression, quality of life, hopelessness, and functional status in this patient population.

Detailed description: The proposed research's primary objective is to study the feasibility of psilocybin therapy for patients with ALS with depressed mood. The secondary objective is to assess its impact on depression, quality of life, hopelessness, and functional status in this patient population. The proposed proof-of-concept interventional trial will use a single-arm design. The study will be an open-label trial in a sample of up to 24 treatment-seeking patients with a diagnosis of ALS and depressed mood. Participants will complete an 8-week course of study treatment including two psilocybin sessions (15 mg in week 4 and 15 or 25 mg in week 6), with follow-up assessments 1, 3, and 6 months after the final psilocybin session.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 18 years and older.
2. Patients must fulfill ALS El Escorial criteria for possible, probable, laboratory supported probable or definite ALS.
3. Patients with a pulmonary forced vital capacity (FVC) \>60%. The investigators have chosen this measure of function to account for respiratory decompensation during the 6-month longitudinal portion of the study.
4. Patients with ability to swallow tablets by mouth. Participants may have a feeding tube, but must be able to swallow by mouth and cannot use the feeding tube to administer the psilocybin tablet.
5. Clinically significant depressive symptoms as evidenced by an Assessment of Depression Inventory (ADI)-12 score \>22.

Exclusion Criteria:

1. Patients with severe speech impairments, including those who are nonverbal, require assisted speech devices, and those who can only communicate by writing or texting.
2. Patients who are unable to consent for themselves.
3. Patients with tracheostomy or continuous continuous positive airway pressure (CPAP) or BiPAP.
4. Known clinical evidence of frontotemporal dementia.
5. Cardiovascular conditions: corrected QT interval (QTc) \>450 msec, uncontrolled hypertension (i.e., systolic blood pressure (SBP)\> 139 mm Hg, diastolic blood pressure (DBP)\> 89 mm Hg), resting heart rate (HR)\> 90 beats per minute, angina, a clinically significant ECG abnormality (e.g., atrial fibrillation), transient ischemic attack (TIA) in the last 6 months, stroke, peripheral or pulmonary vascular disease (no active claudication).
6. Epilepsy with history of seizures
7. Renal disease (creatinine clearance \<40 ml/min using the Cockraft and Gault equation)
8. Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
9. Females who are pregnant (positive pregnancy test) or nursing, or are not practicing an effective means of birth control (i.e., intrauterine systems/devices, hormonal methods including implant, shot, patch, ring, or oral contraceptive, condom, diaphragm, sterilization, and abstinence).
10. Currently taking medications that interact with psilocybin on a regular (e.g., daily) basis: Atypical antidepressants, such as mirtazapine (Remeron), trazodone (Oleptro), vortioxetine (Brintellix), and vilazodone (Viibryd); Tricyclic antidepressants, such as amitriptyline, imipramine (Tofranil), nortriptyline (Pamelor), desipramine (Norpramin), doxepin, trimipramine (Surmontil), and protriptyline (Vivactil); and Monoamine oxidase inhibitors (MAOIs), such as Selegiline (Emsam), tranylcypromine (Parnate), phenelzine (Nardil) and isocarboxazid (Marplan).
11. Currently taking Nuedexta (dextromethorphan/quinidine combination), efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram (Antabuse), Alcohol dehydrogenase inhibitors, or UGT1A9 inhibitors or UGT1A10 inhibitors such as phenytoin, regorafenib, eltrombopag.
12. Current or history of meeting Diagnostic and Statistical Manual (DSM)-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder
13. Have a first degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or bipolar I disorder.

Primary outcomes:
measure: Feasibility of psilocybin treatment as assessed by number of participants recruited, retained and adhere to treatment
timeFrame: 6 months
Secondary outcomes:
measure: Depressive symptoms as assessed by the Montgomery-Asberg Depression Rating Scale
timeFrame: Baseline, 1 week post psilocybin session, 1 month post psilocybin session
measure: Depressive symptoms as assessed by the and ALS Depression Inventory
timeFrame: Baseline, 1 week post psilocybin session, 1 month post psilocybin session
measure: Impact of psilocybin treatment on quality of life as assessed by the EuroQoL 5-dimension, 3-level (EQ-5D-3L) 5-item ALS Assessment Questionnaire
timeFrame: 6 months
measure: Impact of psilocybin treatment on hopelessness as assessed by the Beck Hopelessness Scale
timeFrame: 6 months
measure: Impact of psilocybin treatment on function as assessed by the ALS Functional Rating Scale-Revised
timeFrame: 6 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Center for Psychedelic and Consciousness Research
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Ambereen K Mehta, MD, MPH, FAAHPM
role: PRINCIPAL_INVESTIGATOR
References: