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Prophylactic Effects of Psilocybin on Chronic Cluster Headache (EPOCH)

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ClinicalTrials.gov Identifier: NCT04280055
Recruitment Status : Unknown
Verified February 2020 by Gitte Moos Knudsen, Rigshospitalet, Denmark.
Recruitment status was:  Recruiting
First Posted : February 21, 2020
Last Update Posted : February 21, 2020
Sponsor:
Information provided by (Responsible Party):
Gitte Moos Knudsen, Rigshospitalet, Denmark

Tracking Information
First Submitted Date  ICMJE February 12, 2020
First Posted Date  ICMJE February 21, 2020
Last Update Posted Date February 21, 2020
Actual Study Start Date  ICMJE January 21, 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 19, 2020)
  • Headache frequency [ Time Frame: Week 6-10 (post drug observation) compared to week 0-4 (baseline observation) ]
    Change in headache frequency in number of attacks/week
  • Resting state FC fMRI analyses [ Time Frame: Day 1 of first psilocybin session to 1 week after last psilocybin session (3 weeks) ]
    Resting state FC fMRI analyses, including hypothalamic FC, comparing baseline and rescan, comparison with healthy control sample, and evaluation of correlation between headache frequency changes and FC changes.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2020)
  • Proportion of reduced frequency [ Time Frame: Week 6-10 (post drug observation) compared to week 0-4 (baseline observation) ]
    Proportion of patients with a 50% reduction in headache frequency
  • Headache intensity [ Time Frame: Week 6-10 (post drug observation) compared to week 0-4 (baseline observation) ]
    Change in average headache intensity of attacks (0-10 on Visual Analog Scale (VAS), where 0 is no pain and 10 is worst pain imaginable)
  • Need of acute therapy [ Time Frame: Week 6-10 (post drug observation) compared to week 0-4 (baseline observation) ]
    Number of attacks requiring acute therapy
  • Sideeffects [ Time Frame: Whole observation period (10 weeks) ]
    Proportion of patients experiencing serious side effects
  • Remission [ Time Frame: Day 1 after first psilocybin session until 12 month follow up (1 year). ]
    Proportion of patients with remission lasting more than 1 month
  • Remission duration [ Time Frame: Day 1 after first psilocybin session until 12 month follow up (1 year). ]
    Duration of induced remission (number of weeks)
  • SF-36 [ Time Frame: Week 6-10 (post drug observation) compared to week 0-4 (baseline observation) ]
    Quality of life assessed by questionnaires: The Short Form (36) Health Survey. SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
  • Preferred treatment [ Time Frame: Whole observation period (10 weeks) ]
    Proportion of patients that prefers to continue with psilocybin if this was an option or want to return to usual prophylactics.
  • Mood [ Time Frame: Pre-psilocybin (week 1 and 5) vs post-psilocybin (week six and eight). ]
    Changes in mood measured be the POMS questionaire.
  • Sleep quality [ Time Frame: Pre-psilocybin (week 1 and 5) vs post-psilocybin (week six and eight). ]
    Sleep quality measured by the PSQI questionaire.
  • Depressive symptoms [ Time Frame: Pre-psilocybin (week 1 and 5) vs post-psilocybin (week six and eight). ]
    Depressive symptoms measured by the MDI questionaire.
  • Stress [ Time Frame: Pre-psilocybin (week 1 and 5) vs post-psilocybin (week six and eight). ]
    Perceived stress measured by the PSS questionaire.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prophylactic Effects of Psilocybin on Chronic Cluster Headache
Official Title  ICMJE Prophylactic Effects of Psilocybin on Chronic Cluster Headache: an Open-label Clinical Trial and Neuroimaging Study
Brief Summary The purpose of this study is to investigate the prophylactic effects of psilocybin in chronic cluster headache. Subjects will receive a low dose of psilocybin during 3 sessions spaced by one week. Subjects will maintain a headache diary prior to, during, and after the administrations in order to document headache frequency, intensity and duration. Subjects will undergo a fMRI scanning before the first and after the last psilocybin session.
Detailed Description

Cluster headache (CH) is one of the most painful conditions known. CH affects 1 out 1000 and exists in two well-defined forms: episodic (ECH) and chronic (CCH). Ten to fifteen percent of patients have CCH and have less than three months of pain-free time during a year. Medical treatment for CH is divided into acute abortive treatment for the single attack and a prophylactic treatment. The most commonly used prophylactic, verapamil, decreases attack frequency but does not induce remission and very high doses are needed. Although most therapeutic options ameliorate CH, they may be problematic due to major side effects, unsatisfactory treatment response or availability. Thus, novel treatment options are needed. According to several studies, patients that self-medicate with low doses of the serotonin 2A receptor (5-HT2AR) agonist and psychedelic psilocybin report that this is effective as CH prophylaxis or even to induce remission. So far, no clinical trials to confirm this have been conducted, nor is there any objective measures of brain function in association with psilocybin intake in CH. There is, however, already some evidence from functional magnetic resonance (fMRI) imaging studies suggesting that CH patients have abnormal functional connectivity patterns involving the hypothalamus and distributed brain networks, but the implication of these abnormalities is unknown.

The investigators are conducting a prospective pilot study, evaluating prophylactic effects of psilocybin in CCH using an open-label study design. They're also going to investigate psilocybin's active metabolite psilocin and brain function (fMRI) to identify possible brain mechanisms underlying CCH and treatment response, including the correlation of treatment response with psilocin levels and estimated 5-HT2AR occupancy and the extent to which brain network changes are affected by psilocybin and correlated with treatment response.

Effects of psilocybin on headache frequency, duration and intensity will be assessed in a sample of 20 patients with CCH. Participants will fill out headache logs during the entire study period, in total 10 weeks. Before study inclusion, participants taking prophylactic medication will first go through a 2-week wash-out period to allow for elimination of the medicine. Inclusion is followed by a baseline observation period lasting four weeks, after which patients will first undergo a baseline rs fMRI scanning followed by the first dose of 0.14 mg/kg psilocybin p.o. Blood samples will be collected during the first psilocybin intervention to establish psilocin plasma concentrations, which will be used for estimating receptor occupancy. Participants will then undergo two additional psilocybin administrations spaced by one-week. The last psilocybin dose will be followed by 4 weeks of observation. One week after the last administration of psilocybin, participants will undergo a follow-up MRI scan. Participants will be contacted 3, 6 and 12 months after the last psilocybin dose to gain information about the duration of potential remission periods. All regular acute treatments are permitted during the study period and a systematic record hereof has to be noted in the headache diary. No other prophylactic medication is allowed during the trial and at least a two-week washout period before inclusion is required. Prophylactics are allowed again after the 4 weeks follow-up, with dose and type carefully recorded. Participants will fill out questionnaires during the observation period, in conjunction with psilocybin interventions and at follow-up.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cluster Headache
Intervention  ICMJE Drug: Psilocybin
0.14 mg/kg p.o. in three sessions spaced by one week
Study Arms  ICMJE Experimental: Psilocybin
Intervention: Drug: Psilocybin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: February 19, 2020)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age between 18 and 65
  • A diagnosis of chronic cluster headache according to IHCD-III.
  • Ability to separate cluster headache attacks from other types of headache.
  • A history of at least 4 attacks/week in the last 4 weeks before inclusion

Exclusion Criteria:

  • A history of using a serotonergic hallucinogen for CH.
  • Participation in any clinical trials within 30 days preceding study enrollment.
  • Use of other prophylactic CH medication within the last two weeks.
  • Current use of drugs suspected to interfere with treatment (e.g. antipsychotic medication) or to be hazardous in combination with psilocybin.
  • Presence of other trigeminal autonomic cephalalgias.
  • Known hypersensitivity/allergy to multiple drugs (including psilocybin).
  • A history or presence of any medical and psychiatric condition that might render patient unsuitable for participation.
  • Present or previous manic or psychotic disorder or critical psychiatric disorder.
  • Current drug or alcohol abuse.
  • MRI Contraindications.
  • Pregnancy or breastfeeding
  • Not using safe contraception (if fertile woman)
  • Stroke (<1 year from inclusion)
  • Myocardial infarction (<1 year from inclusion)
  • Hypertension (> 140/90 mmHg at inclusion)
  • Clinically significant arrhythmia (<1 year from inclusion)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04280055
Other Study ID Numbers  ICMJE H-18040896
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Via database of Center for integrated Molecular Brain Imaging (CIMBI) data will be available for neuroscience research community contingent on approval by scientific board.
Responsible Party Gitte Moos Knudsen, Rigshospitalet, Denmark
Study Sponsor  ICMJE Gitte Moos Knudsen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Gitte Moos Knudsen, MD, DMSc Neurobiology Research Unit, Rigshospitalet
PRS Account Rigshospitalet, Denmark
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP