Clinical Trials and Medication Development Projects


Duloxetine for Depressed Substance Abusers
Suzette Glasner-Edwards, Ph.D., Principal Investigator (sglasner@ucla.edu)
Richard A Rawson, Ph.D., and Walter Ling, M.D., Co-Investigators

This pilot study examines the efficacy of duloxetine combined with group psychotherapy for individuals with stimulant dependence and comorbid major depressive disorder. Although the past decade has seen new pharmacological and psychological interventions producing improvement in substance use outcomes, few studies have systematically explored the efficacy of these approaches in combination in patients with substance use disorders and comorbid mental health disorders. This open-label trial will include 20 dually diagnosed individuals with stimulant dependence and Major Depressive Disorder. We will examine the efficacy of 12 weeks of treatment with duloxetine and group psychotherapy on outcomes for depression and substance use. The primary hypothesis is that duloxetine in conjunction with psychotherapy will produce reductions in depressive symptoms and stimulant use. This is an open-label, prospective pilot study without an active comparator or placebo arm. The preliminary data gathered in this investigation will inform the potential significance and feasibility of a subsequent randomized, controlled trial for treatment of depressed adults with concomitant substance use disorders.

Duloxetine For Depressed Substance Abusers was funded by the Eli Lilly Corporate Center, Contract number: F1J-US-X046 (October 2007 to September 2009).


Mindfulness-Based Relapse Prevention for Stimulant Users
Suzette Glasner-Edwards, Ph.D., Principal Investigator (sglasner@ucla.edu)
Richard Rawson, Ph.D., Larissa Mooney, M.D., Co-Investigators

The objective of the current research is to improve treatment for stimulant dependence by augmenting traditional relapse prevention therapy with innovative meditation-based strategies to promote affect regulation skills. Based on Mindfulness-Based Cognitive Therapy for depression (Segal, Teasdale, & Williams, 2002), Marlatt and colleagues recently developed a manualized intervention for the treatment of substance using populations: Mindfulness Based Relapse Prevention (MBRP). The specific aims of this research are 1) To conduct a pilot randomized clinical trial comparing MBRP relative to a health education (ED) control group in stimulant users receiving contingency management (CM). 2) To test the impact of MBRP compared to ED on negative affect, stimulant use, and healthcare outcomes. 3) To evaluate the differential effects of MBRP versus ED on HIV-risk behavior of participants, and 4) To examine potential mechanisms of action of MBRP, including reductions in stress reactivity and biological indicators of arousal (e.g., blood pressure and heart rate).  We hypothesize that MBRP will be more efficacious than ED in reducing negative affect and stimulant use. Further, we expect that MBRP will produce greater reductions in HIV-risk behaviors, stress reactivity, and arousal, and these changes will be associated with substance use outcomes. By providing coping skills to address affect regulation and stress reactivity, two important factors in stimulant relapse, MBRP may provide a promising augmenting strategy for the treatment of stimulant users.

Mindfulness-Based Relapse Prevention for Stimulant Users was funded by the National Institute on Drug Abuse, grant 1 R21 DA029255, from April 2010 to March 2012.


Motivational Therapy for Substance Users with Depression
Suzette Glasner-Edwards, Ph.D., Principal Investigator (sglasner@ucla.edu)
Anne Bellows, Project Director

This study examines the incremental efficacy of an aftercare psychosocial treatment program of a motivational intervention combined with cognitive behavioral therapy (CBT), relative to standard care or treatment as usual (TAU) for individuals with alcohol or drug dependence and comorbid major depressive disorder. Although the past decade has seen new cognitive and motivational interventions producing improvement in substance use outcomes, few studies have systematically explored the efficacy of these approaches in combination in patients with substance use disorders and comorbid mental health disorders. This randomized psychosocial clinical trial will include 80 dually diagnosed individuals with alcohol or drug dependence and a substance-independent diagnosis of Major Depressive Disorder. Among patients receiving pharmacotherapy for depression, we will compare 12 weeks of CBT combined with motivational therapy (CBT-MT) to 12 weeks of treatment-as-usual (TAU) on 6-, 12-, and 24-week outcomes for depression, substance use, HIV-risk behaviors, and other healthcare outcomes. The primary hypothesis is that CBT-MT will produce better outcomes than TAU. We will also examine predictors of early attrition and treatment retention and examine neuropsychological predictors of treatment retention and outcome. The results of this study might provide a dual-diagnosis specific, cognitive-motivational alternative to traditional aftercare programs for the treatment of stimulant users with depression.   

Motivational Therapy for Stimulant Users with Depression was funded by the National Institute on Drug Abuse, Grant 1 K23 DA020085 (September 2007 to August 2012).


The National Drug Abuse Clinical Trials Network
Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Richard A. Rawson, Ph.D., Larissa Mooney, M.D., & Steven Shoptaw, Ph.D., Co-Investigators
Albert L. Hasson, M.S.W., Project Director

As one of 13 Regional Research Training Centers, ISAP is nearing the end of its 11th year as the Pacific Region Node of NIDA’s Clinical Trials Network (CTN), and continues to collaborate with local community treatment programs in an effort to make substance abuse research more relevant to the treatment community. The Betty Ford Center, Bay Area Addiction Research and Treatment, Inc., Les Kelly Family Health Center, Matrix Institute on Addictions, Hina Mauka Treatment Programs, Tarzana Treatment Center, and newcomer, South Bay Treatment Center are participants within the Pacific Region Node helping to guide the CTN research portfolio.

The Pacific Region Node continues to take an active role in the Clinical Trials Network. In addition to leading a 9-site trial comparing the impact of Suboxone and methadone on liver function in treatment-seeking opioid-dependent individuals, “Starting Treatment with Agonist Replacement Therapies” (START), ISAP co-led a project evaluating Suboxone with and without enhanced medical management in the detoxification of prescription opioid users. “Prescription Opioid Addiction Treatment” (POAT) completed subject recruitment in 2009 with the main findings publication currently in review. Launched in the fall of 2008, “Twelve Step Facilitation: Evaluation of an Intervention to Increase 12-Step Involvement and Improve Substance Abuse Treatment Outcomes” evaluating the degree to which a group-based 12-Step Facilitation (TSF) intervention, integrated into treatment as usual (TAU), improves substance-related outcomes completed subject recruitment at the Hina Mauka, Kaneohe facility. Two other CTN protocols scheduled to begin during the summer of 2010 are CTN 0044, evaluating the addition of a web-based intervention to face-to-face counseling, which will begin participant recruitment at the Hina Mauka, Waipahu location, and CTN 0046, evaluating a smoking cessation intervention for individuals receiving treatment for methamphetamine addiction to be implemented at the Matrix Institute on Addictions, Rancho Cucamonga location, and the Tarzana Treatment Center. Currently in development is the “Cocaine Use Reduction using Buprenorphine” (CURB) protocol, which will be led by Drs. Walter Ling and Larissa Mooney of the Pacific Region Node, along with Dr. Andrew Saxon of the Pacific Northwest Node. Recruitment for this project is scheduled to begin in the spring of 2011.
(Additional information is available at www.uclaisap.org/ctn/index.html.)

The National Drug Abuse Clinical Trials Network was funded by the National Institute on Drug Abuse, Grant 2 U10 DA13045 (September 2005 through August 2010).


PRO 807: An Open Label, Multi-Center Extension Study of
Probuphine in Patients with Opioid Dependence
Walter Ling, M.D., Principal Investigator (lwalter@ix.netcom.com)
Catherine Domier, M.A., Project Coordinator

This study provided an opportunity to evaluate participants who received 24 weeks of investigational treatment for opioid dependence with Probuphine® for an additional 6-month trial.  Probuphine® is a product that is inserted into the inner side of the upper arm.  Each Probuphine® implant is about the size of a matchstick and contains buprenorphine HCL and ethylene vinyl acetate (EVA [a type of plastic]). Probuphine® is designed to release buprenorphine, a medication already approved by the FDA for the treatment of opioid dependence, into the body continuously for up to 6 months.

Study participants received four implants with active study medication, and received supplemental Suboxone if clinically indicated.  Safety, pharmacokinetics, and efficacy measures were collected over the 24-week period, and participants were seen a minimum of 12 times. At the end of the treatment period, the  implants were removed, and participants returned for a follow-up visit 2 weeks later.  (Additional information is available at http://theaddictionstudy.com/locations.php.)

PRO 805: A Randomized, Double-Blind, Placebo-controlled, Multi-Center Study of Probuphine in Patients with Opioid Dependence was funded by Titan Pharmaceuticals, Inc., Contract 20054064 (January 2007 to March 2009).


PRO 806: A Randomized, Placebo and Active-Controlled, Multi-Center Study of Probuphine in
Patients with Opioid Dependence

Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Jacqueline Fahey, M.A., Project Director

This study was a randomized, placebo- and active-controlled, multi-center study to assess the effectiveness of Probuphine (buprenorphine hydrochloride/ethylene vinyl acetate), an implantable formulation of buprenorphine hydrochloride (HCl) under development for the treatment of opioid dependence. Probuphine is inserted subdermally into the inner side of the subject's upper arm, in a brief in-office procedure under local anesthetic, and is designed to provide sustained release of BPN for 6 months.  Each Probuphine implant consists of 80 mg of BPN HCl that has been blended and extruded with ethylene vinyl acetate (EVA). Each placebo implant consists of extruded ethylene vinyl acetate (EVA).  Both the Probuphine and placebo implants are sterile and measure approximately 26 mm in length and 2.5 mm in diameter. Across all sites, approximately 250 subjects from 20–25 clinical centers who met eligibility criteria were randomized to 1 of 3 treatment groups in a 2:1:2 ratio [Group A: 4 Probuphine implants (n=100); Group B: 4 placebo implants (n=50); Group C: 12–16 mg/day SL BPN (n=100)], for 24 weeks of treatment. 

PRO 806: A Randomized, Placebo and Active-Controlled, Multi-Center Study of Probuphine in Patients with Opioid Dependence was funded by Titan Pharmaceuticals, Inc., contract 20080840, from April 2010 to March 2011.


Sustained-Release Methylphenidate for Management of
Methamphetamine Use Disorders
Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Maureen Hillhouse, Ph.D., Richard Rawson, Ph.D., Co-Investigators
Shannon Schroeder, B.A., Project Director

This study will evaluate the ability of sustained-release methylphenidate (MPH) to reduce stimulant abuse and increase treatment retention among a 90 individuals seeking treatment for methamphetamine dependence. Thefour-year double-blind, placebo-controlled study includes individuals seeking treatment for methamphetamine dependence, assessed using DSM-IV criteria. Eligible participants are enrolled for an initial two weeks to establish compliance and provide compensation for clinic attendance. After satisfactory adherence to clinic attendance requirements (at least 2 of 4 scheduled days during weeks 1-2), participants are randomized to placebo (n = 45) or MPH (n = 45). Active medication participants receive 18mg MPH/daily for week 3, 36mg/daily for week 4, and 54mg/daily for weeks 5-10. Placebo participants are given placebo prepared to appear identical to active medication. During the active medication phase, all participants will be provided with weekly group sessions of cognitive behavioral therapy (CBT), and motivational incentives (MI) provided for methamphetamine-negative urine test results. After the active medication phase, participants receive placebo (single blind) for the final four study weeks (weeks 11-14), and continue CBT and MI. 

Sustained-Release Methylphenidate for Management of Methamphetamine Use Disorders was funded by the National Institute on Drug Abuse, grant 1 R01 DA025084, from February 2009 to December 2012.


Optimizing Outcomes Using Suboxone for Opiate Dependence
Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Maureen Hillhouse, Ph.D, & Richard Rawson, Ph.D., Co-Investigators
Jackie Fahey, M.S., Project Director

This study is a randomized controlled trial that will test the comparative efficacy of several approaches combining psychosocial treatment with pharmacotherapy for treatment of opioid dependence. In conjunction with buprenorphine pharmacotherapy, psychosocial treatment conditions will include a Cognitive Behavioral Therapy (CBT) condition with medical management (MM), a Contingency Management condition (CM) with MM, a combined CBT+CM condition with MM, and a standard MM condition with neither CBT nor CM, which approximates what physicians do in general when prescribing buprenorphine in their office practice to patients with opioid dependence. Eligible participants will be stabilized on the study drug for a period of 2 weeks and will then be randomly assigned to one of the four conditions for 16 weeks. This first period will be followed by a second 16-week period during which all participants will continue to receive buprenorphine treatment but will not engage in any psychosocial treatment as part of continued study participation. Medical management of the participants will be identical to that delivered during the first treatment phase. At the end of this second 16-week buprenorphine-only treatment period, participants will be tapered off buprenorphine within a maximum of 6 weeks, or will receive referral for continued treatment if unable to successfully complete the taper. Participants will again be assessed at 40-weeks and 52-weeks post-entry into the study. Participants will be 240 opioid-dependent males and non-pregnant, non-lactating females of all racial/ethnic groups who are at least 15 years of age.

Optimizing Outcomes Using Suboxone for Opiate Dependence was funded by the National Institute on Drug Abuse, Grant 1 R01 DA020210 (September 2006 to May 2011).


Medication Development for Stimulant Dependence (MDS)
Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)

Outstanding facilities and appropriately trained staff experienced in the conduct of clinical trials provide UCLA ISAP with a superior reputation in the area of medication development for stimulant dependence. UCLA ISAP serves as one of only a few medication development groups across the nation contracted with the National Institute on Drug Abuse to investigate the effectiveness of new medications for stimulant dependence in Phase I and Phase II research. Each umbrella contract includes a mechanism whereby proposed investigations are offered through a task order to a MDS group for clinical trial research. The specific study is funded according to the pertinent aims, scope, and design of the protocol, and includes a study team led by a principal investigator named by Dr. Ling. Individual studies are typically administered in conjunction with investigators affiliated with the UCLA Department of Family Medicine and the UCLA Department of Psychiatry and Biobehavioral Sciences.

The MDS contract focuses on medication development for stimulant abuse by evaluating medications in the context of carefully metered doses of specific behavioral therapies, by advancing measurement and analysis strategies, and by increasing the efficiency of the clinical trials processes. From extensive research experience conducting medication trials for pharmacological and behavioral treatments for drug dependence, the MDS project contributes to the knowledge base regarding treatments for stimulant abuse. Innovative work has also been possible through collaborative efforts with the UCLA ISAP Center grant for research addressing pharmaceutical treatment for stimulant abuse ( “UCLA Medication Development Unit for Stimulant Abuse”). Until recently, the MDS also served as the umbrella contract for the Methamphetamine Clinical Trials Group (MCTG), tasked with investigating medications specifically for methamphetamine-dependent individuals.

Medication Development for Stimulant Dependence (MDS) was funded by the National Institute on Drug Abuse, Grant N01DA-3-8824 (January 2003 through February 2010).


Double-Blind, Placebo-Controlled Trial of Prometa Pharmacotherapy for the
Treatment of Methamphetamine Abuse
Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Maureen Hillhouse, Ph.D., Project Director

This study assessed the efficacy of the PROMETA pharmacotherapy compared to placebo for initiating abstinence and for preventing relapse to methamphetamine (MA) use in treatment-seeking individuals meeting criteria for MA abuse in multiple treatment locations. The study design included random assignment to pharmacotherapy condition, and both participants and study personnel were blinded to assigned condition. Screening verified participant eligibility and collected demographic, drug use, psychiatric, and neuropsychological information before participants were randomly assigned to either the PROMETA pharmacotherapy condition or to the placebo condition. Pharmacotherapy included 2 infusion phases (starting at Day 0, and again at Day 21) in addition to 40 days of oral medications. Participants were also provided with weekly cognitive behavioral therapy for the duration of the study. Weekly assessments collected information to evaluate medical and psychological status throughout the 15-week study. Drug use outcomes were measured using self-report, verified by biological markers of abstinence (urine tested for metabolites of MA, cocaine, heroin, marijuana, and benzodiazepines). Analyses of participants who received at least one day of medication dosing include 55 participants who received the PROMETA pharmacotherapy and 56 participants who received matching placebo.
(Additional information is available at www.hythiam.com.)

Double-Blind, Placebo-Controlled Trial of Prometa Pharmacotherapy for the Treatment of Methamphetamine was funded by Hythiam, Inc., Clinical Trial 05072347 (March 2005 through December 2008).


A Randomized, Double-Blind, Cross-Over Trial Comparing the Analgesic Potency and Side
Effects of Buprenorphine+Ultra-Low-Dose Naloxone
to Buprenorphine Alone
Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Jessica Jenkins, M.S., Project Director

The objective of this randomized, double-blind, crossover study was to determine whether treatment with IV buprenorphine in conjunction with ultra-low-dose naloxone results in increased analgesic potency, fewer side effects, and reduced opioid tolerance compared to treatment with IV buprenorphine alone.  Twelve participants with lingering pain (rated as 4-7 on a 0-10 likert pain scale) were randomly assigned to treatment order and completed the trial, receiving each drug for 5 days with a 7+ day intertrial interval in which no drug was provided. Analyses of pain scores collected at multiple times on each dosing day show no difference in self-reported pain between the two medications. Additional findings indicate no difference in adverse events between medications. 

A Randomized, Double-Blind, Cross-Over Trial Comparing the Analgesic Potency and Side Effects of Buprenorphine+Ultra-Low-Dose Naloxone to Buprenorphine Alone was funded by the Reckitt-Benckiser, contract 20080605 number (April 2008 to November  2009).


A Phase 2, Double-Blind, Placebo-Controlled Trial of Bupropion for
Methamphetamine Dependence

Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Richard Rawson, Ph.D., Site Principal Investigator
Valerie Pearce, M.P.H., Project Director

This project is a multi-site double-blind, placebo-controlled, parallel-group design study targeting methamphetamine users in which participants are randomly assigned to receive either placebo or bupropion daily for 12 weeks. Participants also receive group Cognitive Behavioral Therapy (CBT) three times weekly along with weekly assessments to collect information on status and functioning. Additional follow-up assessments occur weekly for 4 weeks after completion of study interventions. Eligibility criteria includes methamphetamine use on 29 or fewer days (non-daily use) during the 30 days prior to signing consent.

The primary goal of this study is to assess the efficacy of bupropion in reducing methamphetamine use in participants using methamphetamine on 29 or fewer days during the 30 days prior to signing consent. It is hypothesized that bupropion, compared to placebo, will be associated with an increase in the proportion of subjects who achieve abstinence (confirmed by at least two methamphetamine negative urines) each week during the last two weeks (Weeks 11 and 12) for non-daily users as the primary outcome.

A Phase2, Double-Blind, Placebo-Controlled Trial of Bupropion for Methamphetamine Dependence was funded by the National Institute on Drug Abuse, grant number N01 DA-3-8824, from September 2007 to December 2010.


Aerobic Exercise to Improve Outcomes of Treatment
for Methamphetamine Dependence
Richard A. Rawson, Ph.D., Principal Investigator (rrawson@mednet.ucla.edu)
Christopher Cooper, MD;  Edythe London, PhD, & Larissa Mooney, MD, Co-Investigators
Joy Chudzynski, Psy.D., Project Director (joychud@ucla.edu)

This five-year study, funded by NIDA, seeks to assess the efficacy of aerobic and resistance exercise for the treatment of methamphetamine dependence in a population of 150 individuals in residential treatment. After signing consent and satisfying all inclusion requirements, participants undergo baseline assessments during approximately two weeks of treatment as usual. After randomization, participants enter either the Education condition, consisting of 45- to 50-minute health education sessions three times per week for 8 weeks (n=75), or the Exercise condition, consisting of aerobic and resistance exercise three times per week for 8 weeks (n=75).

The primary goal of the study is to determine whether inclusion of aerobic and resistance exercise within a residential program improves treatment outcomes in terms of reduced methamphetamine use during the first 12 weeks after discharge and at a 26-week follow-up, as well as to characterize effects of exercise on health, psychiatric symptoms and cognition compared to the control (education) group at pre/post intervention.
Of the 150 participants, a subset of voluntary participants will take part in a brain imaging sub-study. This sub-study will use Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) scans to see if cells in the brain change after therapy and treatment for methamphetamine dependence. Specifically, we will see if group participation (exercise or education group) changes the availability of dopamine in the brain.

Aerobic Exercise to Improve Outcomes of Treatment for Methamphetamine Dependence was funded by the National Institute on Drug Abuse, grant 1R01DA027633-01 (September 2009 to August 2014).

Last Updated:  11/16/2011

Top of Page

2016 ISAP Publications
2015 ISAP Publications