Consortia partnerships developing treatments, especially for patients with TBI or PTSD.
by Erin Bolling
It has been eight years since Congress first funded an Army-led research program to address substance abuse, yet it remains an issue that, for many individuals and family members, dwells in the shadows. For those who live with alcohol and substance abuse in their homes, the (ASADRP) to explore potential therapeutic solutions.
The ASADRP looks for integrated approaches to address alcohol and substance abuse disorders, especially those related to traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Through multidisciplinary, team-based efforts, researchers translate basic knowledge into enhanced clinical pharmacological treatments.
A recent Institute of Medicine report, “Substance Use Disorders in the U.S. Armed Forces,” viewed alcohol as the key substance abuse problem in need of intervention and treatment among military personnel.
“The use of alcohol is common in all branches of the military,” said Dr. Ray Santullo, ASADRP program manager. “Furthermore, the National Institute of Alcohol Abuse and Alcoholism reported that 37 percent of those experiencing alcohol abuse also may have a mental health condition.”
PTSD “is a chronic, debilitating anxiety disorder that may develop after direct or indirect exposure to traumatic events,” said Santullo. Recent studies have shown that alcohol dependence and PTSD are highly comorbid—that is, medical conditions that have a high likelihood of existing simultaneously.
PTSD AMONG VETERANS
Among the general population, current rates of PTSD are estimated to be between 3.5 and 8 percent. In comparison, a large-scale investigation of 88,000 veterans serving in the Iraq war found that 12 percent had symptoms of PTSD soon after deployment and 17 percent had symptoms of PTSD at six months post-deployment, which is more than twice the civilian rate.
Along with the current effects of PTSD, approximately 25-30 percent of veterans who served in the Iraq and Afghanistan conflicts may have suffered a mild traumatic brain injury. Evidence indicates that the prevalence of alcohol and other substance abuse disorders from these recent conflicts in veterans with TBI is approximately twice that of veterans who did not suffer TBI.
The “warrior ethos” of the military, which may make some service members reluctant to admit to either mental health or substance abuse problems, can make military personnel less likely to seek help when it’s needed, Santullo said. This challenge has to be taken into account in order to reach the military population that needs help.
The ASADRP is conducting its research at U.S. Department of Veterans Affairs medical centers, as well as military substance abuse treatment centers at Fort Gordon, Georgia, and Naval Medical Center San Diego. By conducting research at these military-specific locations, the program is able to access the appropriate populations and ensure relevant, impactful research.
A BIG-PICTURE APPROACH
“The current services offered to veterans do not adequately address co-occurring substance abuse disorders and PTSD, and there is an immediate need for the development of novel, evidence-based treatments,” Santullo said. “Our goal here is to explore new opportunities addressing alcohol and substance abuse disorders, especially related to TBI and PTSD.”
To achieve this goal, the ASADRP has invested in multidisciplinary teams of leading expert scientists and clinicians, in the form of consortia partnerships. One such partnership is the Pharmacotherapies for Alcohol and Substance Abuse (PASA) Consortium, a collaborative effort with 10 research institutions aimed at bringing new medications to market to treat alcohol and substance use disorders, with a special emphasis on TBI and PTSD in service members and veterans.
This team-based research approach aims to identify promising compounds for use as pharmacotherapies; conduct proof-of-principle research to determine which compounds are most appropriate for human trials; and conduct human proof-of-concept trials with the promising compounds, in order to ultimately provide functional medication to patients.
“The PASA consortium has released three rounds of funding opportunities and five studies are funded: two preclinical discovery studies and three proof-of-concept trials,” said Dr. Rick Williams, PASA principal investigator with RTI International.
Four medications are in preclinical tests for alcohol use disorder and PTSD: doxazosin, developed to treat high blood pressure; zonisamide, an anti-seizure medication; ASP 8062, developed to treat fibromyalgia; and CERC 501, developed to treat depression and substance abuse disorders. Three other compounds are undergoing clinical review: PT 150, developed to treat alcohol abuse; naltrexone, used to treat substance abuse disorders; and buprenorphine, developed to treat opioid addiction.
“We have actively cultivated pharmaceutical company partners who have excellent compounds for alcohol and substance use disorders or PTSD available but need the complement of experts, which the PASA consortium provides, in order to complete human studies to the U.S. Food and Drug Administration’s (FDA) standards,” Williams said.
“Our initial partnerships started with small companies, but our successes in just the last two years have progressed to larger-scale partnerships with companies that can afford to conduct FDA Phase III studies and prepare new drug applications, if our Phase II studies show efficacy,” he said.
The new drug application is the vehicle toward FDA approval and the final step before pharmaceutical sales. The information gathered from these animal and human clinical trials become a part of the application.
To complement these industry collaborations, the Department of Veterans Affairs and the National Institutes of Health are helping to build a strong infrastructure, Williams said, allowing the discovery of new treatments and helping to bridge what is known in translational research as the “valley of death.” These collaborations provide the funding and support needed to cross this valley, allowing medical research to become a new therapy or treatment and ultimately help the patient who needs it.
A CONSORTIUM CASE IN POINT
Another consortium partnership funded by ASADRP is the Institute for Translational Neuroscience, which collaborates with 22 research institutions with expertise in alcohol and drug addiction, PTSD and veterans health.
Dr. Jennifer Mitchell, the consortium’s principal investigator and associate professor at the University of California, San Francisco, said it focuses on rapidly and inexpensively developing therapeutics by identifying and testing compounds that are already approved by the FDA for other indications and could work for alcohol and substance abuse disorders.
“We are currently testing three promising compounds,” said Mitchell. “The first is oxytocin, which is a neuropeptide that is naturally produced in the brain and important for social bonding. Oxytocin can be administered as a nasal spray and has been used to treat a number of indications [mostly related to childbirth] for many years.
“More recent findings suggest that oxytocin can also block some aspects of alcohol intoxication, can decrease alcohol craving and can decrease signs of PTSD,” she continued. “We are trying to gather funds to conduct a Phase III study of oxytocin in people with alcohol use disorder and PTSD, and we hope to someday see this drug readily dispensed to individuals suffering from this comorbidity.”
The second compound the consortium is focusing on is N-acetylcysteine, or NAC, a dietary supplement that builds antioxidants and is typically found in grocery or health food stores. NAC is also FDA-approved to prescribe for other conditions, such as cystic fibrosis or chronic obstructive pulmonary disease. Mitchell explained that strong evidence from both animal and human models shows that NAC can lessen the severity of symptoms of PTSD and alcohol use disorder.
“NAC has been used for many years, and is safe and inexpensive,” said Mitchell. “Our consortium is now completing a series of studies that more thoroughly assess the conditions under which NAC improves mental health and behavior.”
Tolcapone is the third compound that the consortium is investigating. Typically used to help patients with Parkinson’s disease, tolcapone inhibits the degradation of the neurotransmitter dopamine, which allows dopamine to act longer in certain parts of the brain, helping to regulate movement and emotion.
“Recent research shows that administration of tolcapone can help people that struggle with impulsivity and alcohol abuse,” said Mitchell. “We hope that additional studies with tolcapone will help us determine the best dose to use to help people who are trying to control their alcohol consumption.”
PROGRESS IN PARTNERSHIPS
As well as the partnerships among experts in the research field, CDMRP involves patients, survivors, family members and caretakers in the scientific review process. These individuals are selected through a three-step process that includes nomination by an advocacy organization, submitting an application and completing an interview. This integration of consumers with firsthand experience of a disease, injury or condition provides a depth of knowledge and contributes a human dimension to the research.
Retired U.S. Coast Guard Lt. Thomas Faulkenberry served as a consumer reviewer on the ASADRP programmatic panel for vision setting. Consumer reviewers such as Faulkenberry sit along with scientists on both the programmatic and peer review panels, and have full voting member status. These meetings provide an opportunity to harness the consumer’s personal experience to focus the program’s goals.
He welcomed the opportunity to advocate for other service members as part of his transition out of the military. “The research is fascinating to me. I like to know the pros and cons of a medication, as well as alternatives to medication in treating the common disorders in afflicted service members,” he said. “I found the recent development that not enough healthy service members were available to launch a study eye-opening, but it was also an indicator that much more work needs to be done to observe progress. However, it also makes me want to fight harder to help a community that would give everything to know they are well and able to stand a taut watch,” Faulkenberry said, using an expression that’s common in the sea services.
Since its establishment in 2010, the ASADRP has been working to address the research gaps in treatment for substance abuse. The program has many exciting opportunities looking into effective medications for different substances of abuse with and without comorbidities such as PTSD. Additionally, the program is testing a variety of nonpharmacological approaches—including mindfulness, hypnosis and meditation—to treating pain and comorbidities in military and veteran populations.
The ASADRP’s approach to multidisciplinary, team-based research combines experts in the field to develop actual treatments with the patients who need them, here and now. Williams and Mitchell are examples of how consortia work together to develop solutions.
“It can be difficult to work to improve the public perception of drug and alcohol use and PTSD and to engender greater compassion for those suffering from these conditions,” said Mitchell. “If someone has a visible disability from combat, it can be relatively straightforward to feel that they deserve our help and patience. But those who carry trauma and emotional wounds that affect their mental health are more frequently discounted.
“We are so very grateful to the DOD for support of our consortium,” she said. “These aren’t typically the kinds of drugs that drug companies are interested in developing, so we need to be creative in funding our therapeutic pipeline and generating greater support for these debilitating and all too common conditions.”
For more information on the ASADRP activities and other CDMRP research programs, go to http://cdmrp.army.mil/.
ERIN BOLLING of Ripple Effect Communications Inc. is the public affairs specialist for CDMRP, located at Fort Detrick, Maryland. She holds a bachelor of fine arts in graphic design from Shepherd University and an associate of arts in visual art from Hagerstown Community College. She has provided public affairs support within the U.S. Army Medical Research and Materiel Command for more than nine years and is a member of the Public Relations Society of America.
This article will be published in the January – March 2019 issue of Army AL&T magazine.
Subscribe to Army AL&T News – the premier online news source for the Army Acquisition Workforce.