| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10002646 |
| E.1.2 | Term | Anorexia |
| E.1.2 | System Organ Class | 100000004861 |
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| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10002649 |
| E.1.2 | Term | Anorexia nervosa |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 primary aim of the study is to assess the efficacy and feasibility of psilocybin in the treatment of Anorexia Nervosa. |
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| E.2.2 | Secondary objectives of the trial |
| As a secondary aim, we wish to use Magnetic Resonance Imaging (MRI) and electroencephalography (EEG) to examine the neuronal underpinnings of treatment with psilocybin in this patient group. |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Next-Of-Kin study-
Version 1, Date, 18/02/2020
As well as asking that we are in contact with patients’ next of kin/significant other throughout the trial, we will also ask for their ratings of the patient's eating disorder symptoms both via a brief questionnaire and a semi-structured interview. The questionnaire will be sent to participants via email both before the patient begins the trial (between screening and baseline) and 2 weeks after the final dosing session, corresponding to the patient’s follow-up visit. The Next-Of-Kin Questionnaire is a short questionnaire comprised of Likert scales that will be quick to complete. The interview will be performed approximately 2 weeks after the final dosing session. With consent from the participant (the next-of-kin), these interviews will be audio recorded. Patients and their next-of-kin will be made aware that although contact with the next-of-kin is required as part of the trial, participation in the next-of-kin study (i.e., the questionnaire and interview) are not.
The procedures for obtaining an assessment from a significant other will be as follows: at screening, the patient will be asked if they consent to us contacting their next-of-kin (a relevant item is included in the consent form). We will ask for the name and email address of their next-of-kin. We will contact this person by email to explain that they have been identified as the participant’s next-of-kin and that we ask for their involvement in two ways. Firstly, as part of the trial we will maintain contact with them throughout. In addition, we will inform them that we are recruiting for a study involving a questionnaire (to be filled in twice) and an interview. Through the interview and the questionnaire, we will ask about a person they know who is in one of our trials. At the same time, they will be sent an information sheet and consent form to consider. Consent for the first part of this study (contact throughout the trial) is mandatory for the participant to take part in the clinical trial. Consent for the second part (to fill out the questionnaires and take part in the interview) is optional. Once they have completed the consent form and returned it to us, we will send the pre-study questionnaire to those who consent. We will explain that we will contact them via email at some point in the next six months to complete another rating.
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| E.3 | Principal inclusion criteria |
• DSM-V diagnosis of Anorexia Nervosa
• >3 years of illness diagnosis
• Current or past treatments have not been successful to maintain remission
• 21-65 years old
• Female
• Be in the care of a specialist eating disorder team in the UK
• Have a GP and/or specialist eating disorder team in the UK who can confirm diagnosis
• Sufficiently competent in English and mental capacity to provide written informed consent
• BMI >15kg/m2 and medically stable
• Capacity to consent
• Agree to have us maintain contact with an identified next-of-kin for the duration of the study
• Agree to have us maintain contact with their specialist eating disorder team/care team as required for the duration of the study
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| E.4 | Principal exclusion criteria |
• Current or previously diagnosed psychotic disorder
• Immediate family member with a diagnosed psychotic disorder
• Unstable physical condition e.g., rapid weight loss > 2kg in the prior month
• Abnormal serum electrolytes, raised cardiac enzymes, hepatic or renal dysfunction
• Medical condition that is unsuitable for the EEG components of the study (e.g., epilepsy, severe migraine)
• Other physical conditions that are unsuitable for the psychedelic component of the study (e.g., diabetes, epilepsy, severe cardiovascular disease, hepatic or renal failure e.g., CrCl < 30ml/min etc)
• MRI contraindications
• Have a history of laxative abuse in the last 3 months (defined as laxative use more than twice a week for 3 months)
• History of serious suicide attempts or presence of a suicide/ serious self-harm risk at screening
• Currently an involuntary patient
• Significant history of mania (determined by study psychiatrist and medical records)
• Emotionally unstable personality, or other psychiatric problem that the screening clinician feels may jeopardize the therapeutic alliance and/or safe exposure to psilocybin
• Blood or needle phobia
• Positive pregnancy test at screening or during the study, or woman who are breastfeeding
• If sexually active, participants who lack appropriate contraceptive measures
• Drug or alcohol dependence within the last 6 months
• No email access
• Patients presenting with abnormal QT interval prolongation at screening or with a history of this (QTc at screening above 470ms)
• Patients who are currently, or have recently (within 6 months) been enrolled in another CTIMP.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Eating Disorder Examination interview and questionnaire
Readiness and Motivation Questionnaire |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
The EDE will be measured at baseline and at the primary endpoint (6 weeks later). It will then be assessed 6 months after the final study visit.
The EDE-Q and RMQ will be assessed at baseline and every 2 weeks until primary endpoint. They will then be assessed monthly for 6 months after the final study visit, and again at 12 months post the final study visit. |
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| E.5.2 | Secondary end point(s) |
Measures collected at baseline and primary end-point
Measures followed by a ^ will only be completed at primary end-point.
Measures followed by a * will also be completed monthly for 6 months and at 12 months following the final study visit.
Structured interviews and self-report questionnaires completed in person or over the phone:
o Eating Disorder Examination (EDE)*
o Yale-Brown Cornell Eating Disorder Scale Self Report Questionnaire (YBC-EDS-SRQ)
o Yale-Brown Cornell Eating Disorder Scale (Y-BCEDS)
o Relaxed Beliefs Under Psychedelics Questionnaire (REBUS-Q self-constructed)
o Adverse Childhood Experience Questionnaire (ACE)
Self-report questionnaires completed remotely:
o Eating Disorder Examination Questionnaire (EDE-Q)*
o Readiness and Motivation Questionnaire (RMQ)*
o The Pros and Cons of Anorexia scale (P-CAN)*
o Self-Starvation Scale (SS)
o Clinical Impairment Assessment (CIA)*
o Snaith-Hamilton Pleasure Scale (SHAPS)
o Ruminative Response Scale for Eating Disorders (RRS-ED)
o Warwick-Edinburgh Mental Well-being Scale (WEMWBS)
o State Trait Anxiety Inventory- Trait (STAI)
o Quick Inventory of Depressive Symptomology 16 item (QIDS)*
o Flourishing Scale (FS-8)
o Modified Tellegen Absorption Questionnaire (MODTAS)
o Credibility/Expectancy Questionnaire
o Self-esteem: Rosenberg Self-Esteem Scale [4-items] (RSE)
o Psychological Insight Scale (PIS, self-constructed)^
o Selected Items from the Absorption in Music Scale (AIMS - revised)
o Intolerance of Uncertainty Scale
o Watts Connecteness Scale (self-constructed)
o Experiential Avoidance Questionnaire
o The Exercise Habits Questionnaire (self-constructed)
o The Eating Habits Questionnaire (self-constructed)
o The Compulsive Exercise Test
o Multidimensional Psychological Flexibility Inventory (MPFI)
o Meaning in Life Questionnaire (MLQ)
o 2-item Sexual Perceptions Questionnaire (SPQ, self-constructed)
o Selected items from the Self-Report Assessment of Female Sexual Function
o Selected items from the 44-item Big Five Inventory
o The Centrality of events scale (short version)^*
o Single item assessing meaning making^*
Behavioural measures
o Leeds Oxford Food Preference Questionnaire/ task
o Disorder specific tasks
Measures completed around dosing days
The following measures will be completed either prior to treatment either the day before dosing, or on dosing day 1, 2 and 3 or following treatment on the dosing or integration days:
o The Readiness and Motivation Questionnaire (RMQ)
o Eating Disorder Examination Questionnaire (EDE-Q)
o The Pros and Cons of Anorexia scale (P-CAN)
o Multidimensional Psychological Flexibility Inventory (MPFI)
o Spielberger’s Trait Anxiety Inventory (STAI) - State
o The Psychedelic Predictor Scale (self-constructed)
o Mystical Experience Questionnaire (MEQ)
o 11 Dimension Altered States of Consciousness Scale (11D ASC)
o Visual Analogue Scales (VAS)
o Geneva Emotional Music Scales (GEMS)
o The Challenging Experience Questionnaire (CEQ)
o The Emotional Breakthrough Inventory (EBI)
o The Imperial Overview item
o Therapeutic Music Experience Questionnaire (TMEQ, self-constructed)
o Setting Questionnaire (SQ, self-constructed)
o Relaxed Beliefs Under Psychedelics Questionnaire (REBUS-Q self-constructed)
o Experiential Avoidance Questionnaire
o Scale To Assess the Therapeutic Relationship (STAR)
o Psychological Insight Scale (PIS, self-constructed)
Additionally, on dosing days participants will be asked to wear an Empatica E4 wristband to record physiological measurements.
With prior consent, we will also send the patient’s next-of-kin short questionnaires at baseline and at end point to enquire how they perceive the patient’s eating disorder symptoms and whether they have noticed any changes in the patient’s behaviour since the intervention (Section 14).
Neurophysiological/imaging measures
MRI measures will include:
o Anatomical scans such as T1, T2, ASL and diffusion
o Resting state blood oxygen level dependent (BOLD) signal
o Task-based BOLD responses
The EEG measures will include:
o Resting state
o Visual Long-Term Potentiation task60
o Perceptual task
Additional weekly measures will include the weekly QIDS-16, and an eating habits questionnaire (self-constructed).
As this is a feasibility study, we will also be recording recruitment rate and retention rate. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Unless otherwise specified, psychological measures will be collected at baseline and/or at 6 weeks follow-up (primary end point).
MRI measures will be collected at baseline and at the 6 week follow-up (primary end point).
EEG measures will be compared between baseline, on integration days, and the 6 week follow-up (primary end point).
Weekly measures will be collected once a week from screening to the 4 week follow-up (primary end point). |
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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 | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| 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 | No |
| 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 | Yes |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| within subject, single arm |
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| 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 | Yes |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| 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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| The last follow-up phone call and remote questionnaire (up to 12 months after the last study visit) will constitute the end of the study for the last participant. |
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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 | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 3 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 3 |
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