Investigator-Initiated Trials: From Process to Change

MAPS Bulletin 2021: Vol. 31, No. 2

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As MAPS Public Benefit Corporation (MAPS PBC) continues to work toward completing Phase 3 clinical trials and submitting a New Drug Application (NDA) for MDMA-assisted therapy for PTSD to receive prescription approval, the IDEA team have worked to create a beautiful and ever-growing network of investigator-initiated trial (IIT) clinicians whose passion and innovative questioning help to inspire new possibilities within our path to expanding patient access and the conditions that MDMA-assisted therapy may be possible in treating.

By design, investigator-initiated trials (IITs) are unique clinical trials sponsored and implemented by clinicians to investigate a specific product or disease they have interest in furthering within their field. The U.S. Food and Drug Administration (FDA) defines an investigator as “an individual who both initiates and conducts a clinical trial, and under whose immediate direction the investigational drug is administered.” (Klein & Johnson, 2015). The clinician has the responsibility to comply with federal regulations applicable to both the Sponsor and the Investigator.

As both the Sponsor and Investigator, our IIT Clinical Investigators (CIs) take on a daunting feat when they begin the impactful steps towards reaching out to MAPS PBC. By partnering with MAPS PBC for trial oversight support and investigational product (IP), our MDMA-assisted therapy model, an investigator creates opportunities to not only gain experience in FDA regulated research, but to be trained in and introduce psychedelic clinical medicine to their community.

An IIT CI first starts their process with MAPS PBC by submitting a concept proposal. This introduces a specific question within MDMA research or a specific patient population that has not been focused on in psychedelics and has the potential for supporting further proof-of-concept data that might help MAPS PBC find new research pathways to study in the future [1]. IITs also support a more economical approach to conducting research and offer more options for access to patients with some of the most difficult to treat issues.

The IIT team reviews each concept proposal and initiates a discovery call that helps to educate and provide resources to each investigator. MAPS PBC’s IIT team, over the last year, has been working to address the typical barriers that many clinicians face as they begin to develop a passion for exploring their own capacity to treat outside of standard practices. Our discovery calls serve as an introduction to timelines, regulatory requirements, funding, patient access and the institutional/logistical/community support aspects that are required for clinical research. Each of these components, when not thoroughly planned, can prove to be a challenge when conducting IIT research. To support the safe administration and implementation of psychedelic therapy research, we take great care to truly prepare our investigators for what can be a process that takes up to a year or more, from concept proposal to the first participant’s enrollment in an IIT trial.

Once a concept proposal has been supported by the IIT team and approved by the MAPS PBC/MAPS Leadership Team, our IIT team becomes a conduit to navigating and supporting the required aspects the clinician must take on to develop their clinical protocol, implement funding and staffing for the trial, obtain the necessary regulatory approvals and licensure for IP receipt, obtain training for MDMA-assisted therapy administration and trial conduct, set up their clinical site for conducting MDMA research, and meet all FDA sponsor expected trial requirements. IIT research success operates on an investigators willingness to navigate the many layers of sponsor and investigator requirements, the passion to implement their protocol, and on the IIT team’s ability to support the investigator and meet them where they are in their experience and needs.

Many of our investigators find protocol development and funding to be the most difficult aspects of starting an IIT clinical trial. With over 100 concept surveys received to date, it is the goal of our IIT team to help provide the knowledge and process-mapping needed to support the safest and most realistic approach to helping each investigator meet their FDA obligations, while still staying true to the research question within their patient population. As a non-profit benefit corporation, we also understand the challenge of fundraising, so we help to support discovering pathways to funding our IIT study programs when needed. Within the holistic learning approach MAPS PBC takes to IITs, it is each clinician’s innovative questioning, fortitude to push through research challenges, and passion for healing that drives the efforts the MAPS PBC’s IIT team works to infuse into each of our IIT partnerships.

MAPS and MAPS PBC are driven by their passions for education, social justice, economic welfare and health equity for all, with a continued and growing focus on the disparities that continue to plague our globe at a systemic level. We have created a purposeful and unique position as a public benefit and education-based company, to not only impact the field of psychedelics, but to create a web of opportunity and knowledge for both patients and clinicians from many cross-sectional communities and backgrounds, to align on the possibilities psychedelic medicine may hold for them. The COVID-19 pandemic served as a beacon to further open many of our eyes on the depth of the ingrained lack of sufficient healthcare access many minority groups face in our country. Many of our IIT CIs have dedicated their lives to treating within these populations, and despite the challenges COVID placed on practitioners this year, have partnered with us to create IIT trials that we believe may not only provide relief to those who participate in the trial, but also have lasting impacts on diversifying patient access and creating health equity in our society.

To highlight the passion and wealth of possibility displayed within our growing community of clinicians, MAPS PBC is honored to share impact statements from three of our IIT Clinical Investigators currently dedicated to implementing an IIT program with us. Their commitment to innovative research questioning and to healing their patients is invaluable to the work that MAPS PBC does. We are grateful for their support on growing the scientific body of data contributing to furthering psychedelic research and the equitable treatment of mental health in the communities they serve.

Investigators: Willa Hall, Ph.D., Licensed Clinical Psychologist and Casey A. Paleos, MD

Location: Nautilus Sanctuary • New York, NY

IIT Title: An Open Label Study to Treat Post-Traumatic Stress in COVID-19 Health Care Workers Using MDMA-Assisted Therapy

“Our desire to take on an IIT at Nautilus Sanctuary is motivated by our deep appreciation for the transformative healing power of MDMA-assisted therapy and our passion for expanding access to those whose lives stand to profoundly benefit from its effects, but for whom legitimate forms of this therapy remain unavailable outside of a research context. Beyond the direct impact we anticipate this therapy will have on the suffering of our clinical trial participants, we also hope to provide a meaningful volume of practicum experiences and clinical case supervision to recent graduates of the MDMA-assisted therapy training programs, to help populate the ranks of fully qualified MDMA-assisted therapists, who will be in high demand post-FDA approval. We also hope that the data we generate will deepen our understanding of the nature and impact of this work, contribute to its mainstream legitimacy and acceptance, and expand the parameters within which the FDA will permit this work to be conducted post-approval. Finally, our decision to focus on COVID-related post-traumatic stress in health care workers is informed by an intimate understanding of the profound personal cost that is often exacted from caregivers in the act of attending to the suffering of others, particularly under conditions characterized by life-or-death consequences, high degrees of uncertainty and unknown levels of personal danger. These conditions certainly prevailed in the Spring of 2020 as the New York City health care system bravely withstood the brutal brunt of the COVID-19 pandemic’s initial, terrifying incursion into the American continent. Above all else, it is motivated by a deeply felt desire to be of service to our fellow comrades in the health care professions, who have given so freely of themselves in the service of our community in this historic hour of its need.”

Investigator: Lawrence (Larry) Leeman, MD, MPH

Location: University of New Mexico Maternal Child Health Program

IIT Title: MDMA-Assisted Therapy for Postpartum Women with Opioid Use Disorder and Coexisting Post Traumatic Stress Disorder

“My IIT is MDMA-Assisted Therapy for Postpartum Women with Opioid Use Disorder and Coexisting Post Traumatic Stress Disorder. I am a Family and Addiction Medicine physician caring for pregnant women with opioid use and their babies in New Mexico. I have seen a recurring pattern of women relapsing during the first postpartum year, as we have treated their opioid dependence but not the underlying trauma and PTSD. The trauma is often personal and attributable to sexual assault and violence, with the added effects of systemic racism for our primarily Latina and Native population. The addiction and underlying trauma may be transgenerational and epigenetic, as they may have affected the pregnant woman’s family of origin and can now affect her ability to bond with and nurture her newborn. Our objectives are to study the effect of MDMA-assisted therapy on PTSD in postpartum women, the effect of treating PTSD on the likelihood of postpartum relapse of their opioid use, and to observe the effect of treating PTSD on maternal infant-bonding and attachment. We will offer the women the opportunity to bring their infants into the medication sessions about five hours after receiving their MDMA. My awareness of the research on MDMA and PTSD, as well as classic psychedelics for addiction, led me to design and propose this IIT. As part of my preparation for working with psychedelic therapies for addiction, I have taken a partial sabbatical from the University of New Mexico to complete the CIIS Certificate program on Psychedelic Assisted Therapies and Research and participate in research at the University of Wisconsin on Psilocybin and Opioid Use Disorder.”

Investigator: Darron T. Smith, Ph.D., PA-C, DFAAPA

Location: University of Memphis Department of Sociology

IIT Title: Safety, Feasibility, and Preliminary Effectiveness of MDMA-Assisted Therapy Compared to Neurofeedback Training for Race-Based Trauma in African Americans

“In my capacity as an African American healthcare provider, researcher, and educator, I have always been deeply passionate about the plight of stigmatized minority groups in the U.S. and how systemic white racism negatively impacts access to society’s most valued resources and opportunities. More importantly, how race-based mistreatment in the form of daily microaggressions persist, despite Constitutional guarantees that all men and women are created equal. My research on racism has led me to conclude that black antipathy wounds the soul and gets beneath the skin shortening the life span of its victims. The sequela brought about by white imposed systemic racism not only affects physical health, but also brain cognition and function. In other words, the cumulative impact of racism can lead to the development of a debilitating form of race-based posttraumatic stress disorder symptomology or racial trauma. Seeing black family members, friends, students, patients and fellow colleagues recount experiences where race-based microaggressions and the stress it engenders was a call to action for me.

I believe the potential impact of this study will be a greater insight into the relationship between how African Americans live with persistent racial stress ranging from hair touching, name-calling, to police-involved shootings where the victim was black and unarmed. These experiences keep the body in a state of constant fight or flight robbing people of precious mental resources needed to sustain the rigors of life. My deepest wish is that in our study on racial trauma, we find that there is synergy when MDMA is administered with neurofeedback therapy. Given the evidence of neuroplasticity with many hallucinogens such as MDMA, and similar findings in the neurofeedback scientific literature, the brain learns through experience.

We simply do not have enough information regarding how psychedelic substances work with a diverse population. Most studies conducted on hallucinogens over sample white participants with little or no people of color. In this respect, these same studies are somewhat limited in the clinical information gained without a diverse representative sample population to draw from. This opportunity to study racial trauma came about after years of research into the cause and effect of systemic white racism and the need to address the many health consequences. Also, there are not enough scholars doing this kind of work as it was not taken seriously if race was a central factor. The murder of George Floyd brought about greater public awareness to the reality of institutional racism and the unjust and unequal treatment that Africans Americans have faced at the hands of the police for decades. In that moment, I knew this would be a topic worthy of study. I’m grateful to the MAPS organization for sharing my interests and seeing value in diversity and inclusion.”

These clinicians willing to explore and invest in their patients, meeting them where the current scope of treatment may not yet have answers, drive the impact of investigator-sponsored research. IIT research helps provide clinicians room to educate themselves, other providers, and their patients, about what is possible and may provide the answer to potential relief for many other patients who have not had access to supportive medical alternatives, especially those affected by the systemic nature of the development of health equity in our country or who may not have economic access to treatment at all.

The complex web of navigating one’s own mental health care can be an overwhelming and lonely experience, particularly for minority communities or people who have tried many standard-of-care treatments and have not yet found relief. Finding a healthcare provider who is committed to taking the time to walk through the complex web is something every patient seeking solace hopes for. For many people this means opening themselves up to new ideas and treatment modalities that may seem unconventional, but with the right clinician willing to explore and question new potential treatment methods, it could be the difference between sheltering through acute pain and living life again.

Every person has the potential to be affected by IIT research and can support the vital growth and interest needed to continue expanding access to psychedelic therapies. Each of us can invest in prioritizing our mental health and the health of those around us, particularly those suffering from lack of access. Invest time in understanding your own health rights and needs; write to your local legislation regarding state support of healthcare and research grants within your community; talk to your practitioners and loved ones in an open, exploratory, and educational dialogue; get involved in supporting local research in your area through hospitals, community clinics, and universities; and donate to research that is impactful to your community. An investment in investigator research is an investment in the future health of us all.

We extend our gratitude to the research team managing our IIT program: Rebecca Matthews, Hailey Gilmore, M.P.H., and Michael Mithoefer, M.D.

This article features contributions from Michael Mithoefer, M.D., and Hailey Gilmore of MAPS Public Benefit Corporation (MAPS PBC).

Valerie Ahanonu is the former Clinical Program Operations Manager at the MAPS Public Benefit Corporation (MAPS PBC), and led the Pilot, Investigator Initiated and Expanded Access trials Clinical Operations teams in the successful growth and execution of MAPS PBC non-Phase 3 clinical programs.

Valerie has worked as a Sr. Clinical Trial Manager leading global oncology trials in multiple indications and phases (Solid Tumor – Phase I, II; Lymphoma – Phase II; Leukemia – Phase I, II, III, Extension/Compassionate Use, Phase I-II Investigator Sponsored Trials, Pharmacodynamic/ADME, Expanded Access). Throughout Valerie’s career she was able to participate in all aspects of the clinical trial process including global study submissions and global team management, FDA inspection and IND/NDA submissions, as well as operational process and team development.

Valerie received her B.S. in Exercise and Sports Science from the University of Utah in 2009, where she discovered and explored the intricacies of the mind-body connection. Her love for helping people and discovering what makes them tick along with her interest in spiritual growth exploration bolster her passion for clinical research and exploring the soul changing power of psychedelic therapeutics. Valerie is excited to continue moving the needle on more natural and effective mental health treatments that keep the whole person in mind leading to the positive rippling impact we all hope to see in this world!

In her spare time, she enjoys karaoke, gallivanting about the globe with her husband, belly laughing with her family and friends, shaking it like a polaroid picture, gummy bears, skateboarding, French bulldogs and a good TV series with a glass of wine.