Clinical TrialTreatment-Resistant Depression (TRD)PsilocybinRecruiting

Treatment With Psilocybin for Chronic Neuropathic Pain and Depression (TRANSCEND) (TRANSCEND)

This open-label, Phase II trial (n=16) will assess the feasibility, tolerability, and preliminary efficacy of psilocybin (25 mg) therapy for adults with chronic neuropathic pain and treatment-resistant depression (TRD).

Target Enrollment
16 participants
Study Type
Phase II interventional
Design
Non-randomized

Detailed Description

Single-group, open-label Phase II study administering a single oral 25 mg dose of psilocybin with supportive psychotherapy to adults with chronic neuropathic pain and co-morbid treatment-resistant depression to assess feasibility, tolerability, and preliminary efficacy.

Outcomes include safety and tolerability, pain measures (LANSS, PROMIS, pain intensity), and depression severity (HamD-17) with screening, baseline, acute and follow-up assessments.

Participants must be able to taper antidepressant/antipsychotic medication prior to dosing, be medically stable with adequate renal function, and have no personal or first-degree family history of psychotic disorders.

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Therapeutic Protocol

support

Study Arms & Interventions

Psilocybin 25 mg

experimental

Single-group open-label administration of a single 25 mg encapsulated dose of psilocybin with supportive psychotherapy.

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

    Encapsulated HPMC capsule (PEX010); administered once with supportive therapy.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:\n\n1. Adults 18 to 65 years old;\n2. Are outpatients;\n3. Must be deemed to have capacity to provide informed consent;\n4. Must sign and date the informed consent form;\n5. Stated willingness to comply with all study procedures;\n6. Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent;\n7. Primary DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the Structured Clinical Interview for DSM-5 (SCID-5) administered at the first screening visit;\n8. Participants diagnosed with treatment-resistant depression defined as individuals with a baseline HamD-17 score > 14 and that have not responded to two or more separate trials of antidepressants at an adequate dosage and duration (an antidepressant resistance rating score of three or more is considered an adequate trial) based on the Antidepressant Treatment History Form (ATHF) (Sackeim & Sackeim, 2001); there is no upper limit on the number of treatment failures;\n9. Diagnosis of chronic neuropathic pain as determined by a pain specialist and confirmed with the standardized Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaire;\n10. Moderate-to-severe neuropathic pain determined by Patient Reported Outcomes Measurement Information System (PROMIS) Pain Interference score of > 60, as well as mean pain intensity scores > 5 on a numeric rating scale;\n11. Previous trials of at least two medications recommended in the Canadian consensus guidelines on the management of neuropathic pain with no self-reported meaningful improvement in symptoms;\n12. Ability to take oral medication;\n13. Individuals with an eGFR above 40 mL/min/1.73 m2 and all blood work on clinical laboratory tests assessed as not clinically significant by study delegate physician at Screening (V1);\n14. Individuals who are capable of becoming pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation;\n15. Individuals who are willing to taper off current antidepressant and antipsychotic medications for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for the duration of the study and whose physician confirms that it is safe for them to do so; and\n16. Agreement to adhere to Lifestyle Considerations (section 4.5) throughout study duration.

Exclusion Criteria

  • Exclusion Criteria:\n\n1. Pregnant as assessed by a urine pregnancy test at Screening (V1) or individuals that intend to become pregnant during the study or are breastfeeding;\n2. Treatment with another investigational drug or other intervention within 30 days of Screening (V1);\n3. Have initiated psychotherapy in the preceding 12 weeks prior to Screening (V1);\n4. Have a DSM-5 diagnosis of substance use disorder (recreational use of tobacco, alcohol, cannabis and prescribed opioids are permitted) within the preceding 6 months;\n5. Have active suicidal ideation with intent and plan as determined by item 3 of the HamD-17;\n6. Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; obsessive-compulsive disorder, psychotic disorder (unless substance induced or due to a medical condition), bipolar I or II disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history and the SCID-5 clinical interview;\n7. Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition); or bipolar I or II disorder as determined by the family medical history form and discussions with the participant;\n8. Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history, uncontrolled hypertension, low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment;\n9. Presence of baseline prolonged QTc or Torsade de Pointes as measured by the ECG or a history of long QTc syndrome or related risk factors;\n10. Individuals who are currently taking methadone, buprenorphine or > 100 milligrams of morphine (or morphine equivalents);\n11. Any other clinically significant physical illness including chronic infectious diseases or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study.

Study Details

Locations

Centre for Addiction and Mental Health — Toronto, Ontario, Canada

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