Clinical Study Protocol LSD – unterstützte Psychotherapie bei Personen mit Angstsymptomatik in Verbindung mit fortgeschrittenen lebensbedrohenden Erkrankungen. Eine doppelblinde, plazebokontrollierte Phase-II Dosis-Wirkungs- Pilotstudie LSD – assisted psychotherapy in persons suffering from anxiety associated with advanced-stage life threatening diseases. A phase-II, double-blind, placebo-controlled dose-response pilot study Original Protocol Version Date: January 9, 2007 SPONSOR MAPS PRINCIPAL INVESTIGATOR: Dr. med. Peter Gasser; [email protected] Facharzt FMH Psychiatrie + Psychotherapie Hauptbahnhofstrasse 5 4500 Solothurn / Switzerland MEDICAL MONITOR Rick Doblin, PhD; [email protected] ; Office: (1) 617-484-8711 STUDY MONITOR Valerie Mojeiko; [email protected] ; Office (1) 831-336-4325 Mobile (1) 941-726-3672 Fax (1) 831-336-3665 For trial related emergencies out of office hours please contact 617-276-7806 Property of MAPS MAPS Clinical Study Protocol L-DA1 09 Jan. 07 Page 1 of 64 Table of Contents German Summary ...........................................................................................................3 Hintergrund ....................................................................................................................3 Ziel ...................................................................................................................................4 Methode ..........................................................................................................................4 Erwarteter Nutzen des vorliegenden Projektes ..........................................................5 Ethics ..................................................................................................................................6 Informed Consent of Subject ........................................................................................6 Introductory Statement ..................................................................................................7 Study Design ..................................................................................................................9 Objectives: ....................................................................................................................10 Background and Significance ....................................................................................10 General Investigational Plan ......................................................................................12 Investigators .................................................................................................................12 Subjects .........................................................................................................................12 Inclusion Criteria .........................................................................................................13 Exclusion Criteria ........................................................................................................14 Prescreening and Informed Consent .........................................................................14 Subject Numbering ......................................................................................................15 Randomization .............................................................................................................16 Removal of Subjects from Therapy or Assessment ................................................16 Psychotherapy ..............................................................................................................16 Psychotherapy During Experimental Session............................................................17 Open Label Continuation for Active Placebo Patients ..............................................18 Data Analysis ...............................................................................................................19 Drugs and Dosage ........................................................................................................20 Methods ........................................................................................................................20 Assessment / Measures ..............................................................................................23 Monitoring for Risks ....................................................................................................26 Acute Psychological Distress .....................................................................................26 Medical Emergencies ..................................................................................................27 Adverse Events ............................................................................................................28 Serious Adverse Events ..............................................................................................29 Adverse Event Collection ...........................................................................................30 Collection of Concomitant Medications ...................................................................30 Laboratory Assessments .............................................................................................30 Study Monitoring, Auditing and Documentation ....................................................30 Risks to Participants ....................................................................................................31 MAPS Clinical Study Protocol L-DA1 09 Jan. 07 Page 2 of 64 Risks and Discomforts Related to Screening and Baseline Examination..................31 Risks and Discomforts of Psychotherapy ..................................................................31 Risk of the Experimental Drug (LSD).......................................................................31 Panic attacks, severe generalized anxiety, or persisting insomnia.............................32 Self-injurious behavior...............................................................................................32 Psychosis, suicidal thoughts or impulses...................................................................32 Chronic neuropsychological effects...........................................................................33 Reproductive and Developmental Risks....................................................................34 Abuse Liability...........................................................................................................34 Risks of Active Placebo dose of LSD........................................................................35 Alternative Treatment and Procedures ....................................................................35 Risk-Benefits Analysis ................................................................................................35 Confidentiality ...............................................................................................................36 Costs to Participants .....................................................................................................37 Patient’s Rights / Insurance ........................................................................................37 Record Retention ...........................................................................................................37 Chemistry, Manufacturing and Control Information ...........................................38 Pharmacokinetics and Pharmacodynamics .............................................................39 Primary Pharmacodynamics .......................................................................................41 Drug Activity Related to Proposed Action ................................................................41 Safety Pharmacology ..................................................................................................42 Abuse Liability...........................................................................................................44 Pharmacokinetics/Toxicokinetics ..............................................................................45 Absorption, Distribution, Metabolism, Excretion......................................................45 Toxicology ....................................................................................................................47 Acute toxicity.............................................................................................................47 Reproductive Toxicity ...............................................................................................47 Previous Human Experience ......................................................................................48 References .......................................................................................................................49 Signature Page: ..............................................................................................................59 Appendix A: Investigators ..........................................................................................60 Appendix B: Daily Diary - example .........................................................................62 Appendix C: Letter for Recruitment of Participants ............................................63 MAPS Clinical Study Protocol L-DA1 09 Jan. 07 Page 3 of 64 German Summary Hintergrund Nachdem LSD im Jahre 1943 durch den Schweizer Chemiker Albert Hofmann in Basel entdeckt wurde, erfolgte eine fast dreissig Jahre dauernde rege Forschungstätigkeit, die im psychiatrischen