Michael Mithoefer, M.D.

MDMA-Assisted Psychotherapy in the Treatment of Posttraumatic Stress Disorder (PTSD): Tenth Update on Study

15 SUBJECTS HAVE NOW completed my MAPS sponsored Food and Drug Administration (FDA) Phase 2 pilot study evaluating MDMA-assisted psychotherapy for subjects with treatment-resistant posttraumatic stress disorder (PTSD). Six more potential subjects have passed phone screening and are currently scheduled for formal screening. Efficacy data at this stage is promising, so far making a strong case for continuing the research into multisite Phase 3 studies. The Data Safety Monitoring Board (DSMB) met in late January for its final review, now that 15 out of 20 subjects have completed the experimental treatment. The DSMB is comprised of an MD, a Psy.D. and a Pharm.D. not otherwise involved in the study. It reports to MAPS, which forwards the DSMB reports to the institutional review board (IRB) and FDA. The DSMB recommended that the study continue without modification. The DSMB's only safety concern was that those subjects who received the placebo might experience a substantial increase in PTSD symptoms after tapering off of psychiatric medications.

The Internet advertising campaign that MAPS Clinical Research Associates Valerie Mojeiko and Josh Sonstroem developed with the expert help of Martin Polanco has yielded impressive results. Within a few weeks in late February and early March we received inquiries from 14 potential subjects, so we expect to have completed the enrollment for this study by the time of publication. The Internet advertising was so successful that we have discontinued it and are placing potential subjects who pass phone screening on a list of alternates in case we need to replace dropouts. Interestingly, two of the six people now scheduled for formal screening are Iraq veterans, the first veterans we have been able to recruit.

Early this year, we had several months of frustratingly slow recruitment. First, one subject who had passed all the screening except for the blood tests at the time of my previous Bulletin update was not able to be enrolled because her lab results revealed a previously undiagnosed medical problem that required treatment. In addition, another subject dropped out of the study one month after his first MDMA session. His decision to drop out was not related to an adverse event, but was because he lived far away and did not want to spend the additional time away from home that would have been required. He did have a significant improvement in symptom scores after one MDMA-assisted session. He felt he would be able to build on these improvements by continuing to work with his psychologist at home. Because we felt that the limits the IRB had placed on reimbursement of travel expenses had added to the stress this subject experienced we subsequently asked the IRB to allow MAPS to reimburse actual travel and lodging expenses (for economyclass tickets and moderately priced hotels) without an arbitrary upper limit and to add $50 per day for meal expenses for people from out of town. The IRB has agreed to these changes, which we hope will make participation less stressful for future subjects from out of town.

In October 2006, we received permission from the IRB to collect long-term follow-up data on people who complete the existing protocol. We will now be able to re-administer the Clinician Administered PTSD Scale (CAPS) and a questionnaire one year following the subject's last MDMA therapy session (or longer for subjects who have already completed the study more than a year ago). We delayed implementing this follow-up protocol until early March because we linked that request to a request for clarification about the IRB's media policy for our study.

Since the beginning of the study some subjects have expressed a desire to talk to the media about their experience to inform the public about the possible benefits of MDMA as a medicine. At the IRB's request we have asked them to refrain from doing so until the study is completed. With the addition of the longterm follow-up we did not want to be in the position of having to ask people to prolong this period of not speaking to the media for another year or more. In late February, after several years of effort, three rejections, and an appeal, the IRB decided that review of postparticipation interviews falls outside its scope and determined that it has no jurisdiction to control subjects' decisions about whether or not to speak to the media. They did ask us to adhere to the following guidelines, with which we agree:

• That neither sponsors nor investigators should ever disclose information identifying a subject to the media;
• That subjects should be encouraged to refrain from discussing a trial until after their participation has ended;
• That subjects who express an interest in sharing their experiences with representatives of the media may be provided contact information for such representatives by the investigator after the subject has completed their involvement in the study.

We have received inquiries from both print journalists and documentary filmmakers and are in the process of considering which are most likely to skillfully communicate information about our research to the public.

With the recent recruiting success we are in a position to finish the study by the end of 2007. At that point, if efficacy data continues to be promising, we will submit the data to the FDA along with a request for approval of a multisite Phase 3 trial. Upon the study's completion, we will also submit an article for publication in a peer reviewed journal. The long-term followup research will be treated as an additional study and will be reported and published separately when it is complete. We are also in the early design stages of a Phase 1 safety study in psychologically healthy subjects with controlled hypertension, Hep-C, or who are HIV-positive, all medical conditions that currently exclude people from participating in the MDMA/ PTSD study but which we believe do not pose unacceptable risks. We want to explore the use of MDMA in people with these conditions to see if we can safely enroll a wider range of subjects as we move into our Phase 3 studies. ¥