E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic cluster headache. |
Kronisk Hortons (klyngehovedpine) hovedpine |
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E.1.1.1 | Medical condition in easily understood language |
Chronic cluster headache. |
Kronisk Hortons (klyngehovedpine) hovedpine |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056941 |
E.1.2 | Term | MRI brain |
E.1.2 | System Organ Class | 100000004848 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009698 |
E.1.2 | Term | Cluster headaches |
E.1.2 | System Organ Class | 100000004852 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020397 |
E.1.2 | Term | Horton's headache |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of the present open-label trial is to evaluate the effect of psilocybin on chronic cluster headache (i.e., headache frequency). |
Hovedformålet med projektet er at evaluere effekten af psilocybin på hovedpinefrekvensen i kronisk klyngehovedpine (Hortons hovedpine). |
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E.2.2 | Secondary objectives of the trial |
Additional objectives are to 1) evaluate changes in brain function and correlations with potential clinical effects, 2) evaluate the extent to which plasma psilocin levels correlate with clinical effects. |
Yderligere formål er at 1) evaluere om der er forandringer i hjernefunktion, og om forandringer korrelerer med potentielle kliniske effekter, 2) evaluere om plasma psilocinniveauer korrelerer med kliniske effekter. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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•Alder mellem 18 og 65 år •En diagnose for kronisk Hortons hovedpine ifølge IHCD-III. •Evne til at adskille Hortons hovedpine anfald fra andre typer hovedpine. •Mindst 4 anfald/uge i de sidste 4 uger inden inklusion.
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E.4 | Principal 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). •Current use of drugs suspected 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). |
• Tidligere brug af serotonerge hallucinogener for Hortons hovedpine. • Deltagelse i et klinisk forsøg inden for 30 dage forud for inklusion. • Brug af anden profylaktisk medicin inden for forsøgsperioden. • Nuværende brug af stoffer der formodes at kunne interagere med psilocybin behandling (fx antipsykotisk medicin). • Nuværende brug af stoffer der formodes at være farlige i kombination med psilocybin. • Tilstedeværelse af andre trigeminale autonome cephalalgier. • Kendt overfølsomhed / allergi over for flere lægemidler (herunder psilocybin). • Kendt med eller tilstedeværelse af enhver medicinsk og psykiatrisk tilstand, der kan gøre patienten uegnet til deltagelse. • Nuværende eller tidligere manisk eller psykotisk lidelse eller kritisk psykiatrisk lidelse. • Nuværende stof eller alkohol misbrug. • Kontraindikationer for MR-scanning • Graviditet eller ammende. • Brug af ikke sikker kontraception (hvis kvinde) • Apopleksi (<1 år fra inklusion) • Myokardieinfarkt (<1 år fra inklusion) • Hypertension (> 140/90 mmHg ved inklusion) • Klinisk betydende arytmi (<1 år fra inklusion). |
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Change in headache frequency in number of attacks/week. 2.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
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1.Ændring i hovedpinefrekvens (anfald/uge) 2.Resting state funktionel konnektivitetsanalyser (FC), inkl. hypothalamisk FC, sammenligning af baseline og rescan, med raske kontroller og evaluering af korrelation mellem hovedpinefrekvens og FC forandringer. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1.In week 6-10, i.e. the four weeks after the last psilocybin dose, compared to the four-week baseline. 2.At baseline and at MRI rescan. |
1.Uge 6-10 (sidste fire uger efter psilocybin) vs fire ugers baseline. 2.Ved baseline og ved rescan. |
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E.5.2 | Secondary end point(s) |
1.Proportion of patients with a 50% reduction in headache frequency in week 6-10, i.e. the four weeks after the last psilocybin dose, compared to the four-week baseline. 2.Change in average headache intensity in number of attacks/week in week 6-10, i.e. the four weeks after the last psilocybin dose, compared to the four-week baseline. 3.Number of attacks requiring acute therapy in week 6-10, i.e. the four weeks after the last psilocybin dose, compared to the four-week baseline. 4.Proportion of patients experiencing serious side effects. 5.Proportion of patients with remission lasting more than 1 month. 6.Duration of induced remission (number of weeks) 7.Proportion of patients who changes from CCH to eCH. 8.Quality of life assessed by questionnaires: 36-item short-form health survey (SF-36) in week 6-10, i.e. the four weeks after the last psilocybin dose, compared to the four-week baseline 9.Proportion of patients that prefers to continue with psilocybin if this was an option or want to return to usual prophylactics 10.Changes in mood (POMS), perceived stress (PSS), sleep quality (PSQI) and depressive symptoms (MDI) pre-psilocybin (week 1 and 5) vs post-psilocybin (week six and eight).
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1. Andel af patienter med 50% reduktion i hovedpinefrekvens i uge 6-10, dvs. de fire uger efter den sidste psilocybindosis sammenlignet med fire ugers baseline. 2. Ændring i gennemsnitlig hovedpineintensitet i antal anfald per uge i uge 6-10, dvs. de fire uger efter den sidste psilocybindosis sammenlignet med fire ugers baseline. 3. Antal anfald, der kræver akut behandling i uge 6-10, dvs. de fire uger efter den sidste dosis psilocybin sammenlignet med fire ugers baseline. 4.Andel af patienter, der oplever alvorlige bivirkninger. 5. Andel patienter med remission, der varer mere end 1 måned. 6. Varighed af induceret remission (antal uger) 7. Andel af patienter, der skifter fra CCH til eCH. 8. Livskvalitet vurderet ved hjælp af spørgeskemaer: 36-item short-form health survey (SF-36) i uge 6-10, dvs. de fire uger efter den sidste dosis psilocybin sammenlignet med den fire ugers baseline 9. Andel af patienter, der foretrækker at fortsætte med psilocybin, hvis dette var en mulighed eller ønsker at vende tilbage til almindelig forebyggende behandling 10. Ændringer i humør (POMS), opfattet stress (PSS), søvnkvalitet (PSQI) og depressive symptomer (MDI) pre-psilocybin (uge 1 og 5) vs post-psilocybin (uge seks og otte). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3,8. week 6-10, i.e. the four weeks after the last psilocybin dose, compared to the four-week baseline. 4. All study. 5-7,9. All study. Data collection at 3, 6 and 12 months. 10. Pre psilocybin Week 1 and 5 vs post-psilocybin Week six and eight.
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1-3,8. uge 6-10, dvs. de fire uger efter den sidste psilocybindosis sammenlignet med fire ugers baseline. 4. Alle undersøgelser. 5-7,9. Alle undersøgelser. Dataindsamling efter 3, 6 og 12 måneder. 10. Pre psilocybin Uge 1 og 5 kontra post-psilocybin Uge seks og otte. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Changes in brain function as measured with MRI. |
Forandringer i hjernefunktion målt med MRI. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |