Research Findings - CTN-Related Research
CTN Participation Influences Innovation Adoption Beyond Clinical Trial Protocol Activities
Organizational involvement in clinical research may lead to adoption of the focal intervention by participating treatment agencies, but it is not known whether research involvement enhances innovativeness beyond the specific interventions that are tested. The authors studied programs in NIDA's Clinical Trials Network to examine this question. To date, the CTN has conducted multiple trials on buprenorphine, but none on alcohol pharmacotherapies. Using longitudinal data from a pooled sample of CTN programs and public sector treatment programs outside the CTN, the authors examined organizational adoption of tablet naltrexone and acamprosate, with CTN affiliation and buprenorphine study participation as predictors of interest. In multivariate models controlling for a variety of organizational characteristics, CTN-affiliated programs were 3.5 times more likely to have adopted acamprosate, and 3.2 times more likely to have adopted tablet naltrexone during the 2-year interval in which CTN programs were heavily exposed to research on buprenorphine. The authors suggest that participation in research networks may enhance organizational innovativeness generally to include interventions beyond the scope of the network. Abraham AJ, Knudsen HK, Rothrauff TC, Roman PM. The Adoption of Alcohol Pharmacotherapies in the Clinical Trials Network: The Influence of Research Network Participation. J Subst Abuse Treat. 2010; 38: 275-283.
Innovation in the NIDA Clinical Trials Network
The National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) to conduct trials of promising substance abuse treatment interventions in diverse clinical settings and to disseminate results of these trials. Interviews with program administrators in 2002 and 2004 of 262 CTN community treatment programs (CTPs) across 17 CTN regional research centers (nodes) addressed CTN''s formation as a network of inter-organizational interaction among treatment practitioners and researchers. Data from Wave I to Wave II indicated strong relationships of interaction and trust (M=4.35 & 4.40 on a 5-point scale), but a decline in problem-centered inter-organizational interaction over time (from M=2.58 to M-1.72 staff hours/week of communication; p<.01). Second, adoption of buprenorphine and motivational incentives among CTN''s affiliated community treatment programs (CTPs) was examined over three waves of data. In the case of buprenorphine, CTP use rose from 15.5% at baseline to 31.8% at 24 months, and 34.5% at 48 months. However, 4.7% abandoned use at 24 months, and 7% more discontinued at 48 months. Although over time 18.6% of CTPs adopted MI/CM, gains were offset by 17.8% discontinuing MI/CM. Finally, 58.1% of CTPs never used buprenorphine over the four-year period and 38.7% never used MI/CM. Third, CTPs' pursuit of the CTN's dissemination goals were examined. Results indicated that such organizational outreach activities are underway, with 40% of CTPs organizing or leading training sessions for non-CTN CTPs. Considering that CTN interventions are consider state-of-the-art, it is evident that adoption did not approach 100% and that dissemination activities did not involve even half the CTPs. Organizational treatment philosophies and regulatory barriers were commonly cited reasons for non-adoption. Roman PM, Abraham AJ, Rothrauff TC, Knudsen HK. A Longitudinal Study Of Organizational Formation, Innovation Adoption, And Dissemination Activities Within The National Drug Abuse Treatment Clinical Trials Network. J Subst Abuse Treat. 2010; 38 (Suppl 1): S44-S52.
Increasing Prenatal Care and Healthy Behaviors In Pregnant Substance Users
Evidence suggests that prenatal care, healthy behaviors such as exercise and nutrition, and general stress level are associated with fetal and maternal health but there is a relative dearth of research on interventions to improve these factors in pregnant substance users. Two hundred pregnant substance users entering outpatient substance abuse treatment were randomized to receive either three individual sessions of Motivational Enhancement Therapy for pregnant substance users (MET-PS) or the first three individual sessions normally provided by the program (CTN-0013). The present study evaluated the relative efficacy of MET-PS, compared to treatment as usual on modifiable healthy behaviors, and the impact of treatment when the groups were pooled. The results suggest that MET-PS was not more effective than treatment as usual in improving modifiable healthy behaviors. When the treatment groups were pooled, the results suggest that there were significant increases in prenatal care utilization and prenatal/multi-vitamin and water consumption, and a significant decrease in stress. Limitations and recommendations for further research are discussed. Kropp F, Winhusen T, Lewis D, Hague D, Somoza E. J Psychoactive Drugs. 2010; 42(1): 73-81.
Do Therapist Cultural Characteristics Influence the Outcome of Substance Abuse Treatment For Spanish-Speaking Adults?
This secondary data analysis of the Clinical Trials Network's Motivational Enhancement Therapy effectiveness trial with Spanish-speaking substance users (CTN-0021) examined whether the degree of birthplace and acculturation similarities between clients and therapists, as well as the therapists' own level of acculturation and birthplace were related to the clients' participation in treatment and level of substance use during outpatient substance use treatment. Sixteen therapists and their 235 clients from the 480 participants in the larger effectiveness trial were included in the analyses for this study. Results of the multilevel regression models for client participation in substance use treatment and client days of substance use, taking into account within and between therapist cultural characteristics, revealed that birthplace match and acculturation similarity between each therapist and his or her clients did not predict client outcomes. Instead, therapists' birthplace (p < 0.05) and level of acculturation (p < 0.001) independently predicted days of substance use, but not treatment participation for monolingual Spanish-speaking clients. Suarez-Morales L, Martino S, Bedregal L, McCabe BE, Cuzmar IY, Paris M, Feaster DJ, Carroll KM, Szapocznik J. Cultur Divers Ethnic Minor Psychol. 2010; 16(2): 199-205.
HIV Risk Behavior In Treatment-Seeking Opioid-Dependent Youth: Results From A NIDA Clinical Trials Network Multisite Study (CTN-0010)
This study assessed baseline rates of and changes in HIV drug and sexual risk behavior as a function of gender and treatment in opioid-dependent youth. One hundred fifty four participants were randomly assigned to extended buprenorphine/naloxone therapy (BUP) for 12 weeks or detoxification for 2 weeks; all received drug counseling for 12 weeks; 150 participants were eligible for this analysis. HIV risk was assessed at baseline and 4-week, 8-week, and 12-week follow-ups. Behavioral change was examined using generalized estimating equations. Baseline rates of past-month HIV risk for females/males were non significant for injection drug use (IDU), multiple partners, unprotected intercourse and sexual activity. Baseline rates for injection risk were significant (P < 0.001). IDU decreased over time (P < 0.001), with greater decreases in BUP versus detoxification (P < 0.001) and females versus males in BUP (P < 0.05). Injection risk did not change for persistent injectors. Sexual activity decreased in both genders and conditions (P < 0.01), but sexual risk did not. Overall, IDU and sexual activity decreased, particularly in BUP patients and females, but injection and sexual risk behaviors persisted. Although extended BUP seems to have favorable effects on HIV risk behavior in opioid-dependent youth, risk reduction counseling may be necessary to extend its benefits. Meade CS, Weiss RD, Fitzmaurice GM, Poole SA, Subramaniam GA, Patkar AA, Connery HS, Woody GE. J Acquir Immune Defic Syndr. 2010 Apr 13. [Epub ahead of print].
Association of Race and Ethnicity With Withdrawal Symptoms, Attrition, Opioid Use, and Side-Effects During Buprenorphine Therapy
Some studies report differences in opioid withdrawal between racial/ethnic groups. However, it is not known if these differences are reflected in differential treatment response. Data from National Institute on Drug Abuse (NIDA) Clinical Trials Network trial CTN-0003 were used to examine racial/ethnic differences before and during stabilization with buprenorphine. At induction, non-Hispanic Caucasians had higher objective and subjective withdrawal scores and greater opioid craving than minority participants. No significant between-group differences were observed on these scales following buprenorphine. Non-Hispanic Caucasians and Hispanics reported more adverse events than African Americans. Although ethnic and racial differences were observed prior to buprenorphine treatment, scores following buprenorphine treatment were similar between groups. Brown ES, Tirado C, Minhajuddin A, Hillhouse M, Adinoff B, Ling W, Doraimani G, Thomas C. J Ethn Subst Abuse. 2010; 9(2): 106-114.
Survey of Eating Disorder Symptoms Among Women In Treatment For Substance Abuse
A strong association between substance use disorders (SUDs) and eating disorders (EDs) in women has been established. Yet, little is known about the rates and impact of ED symptoms in women presenting to addiction treatment. The current investigation assessed the prevalence of ED symptoms and their effect on treatment outcomes in a sample of substance abusing women with co-occurring posttraumatic stress disorder (PTSD) enrolled in outpatient substance use programs. Participants were 122 of the 353 women who participated in a multisite clinical trial (CTN-0015) comparing two behavioral treatments for co-occurring SUD and PTSD. The Eating Disorder Examination-self report, and measures of PTSD and SUD symptoms were administered at baseline, during treatment and at four follow-up points. Two subgroups emerged; those reporting binge eating in the 28 days prior to baseline (Binge group; n = 35) and those who reported no binge eating episodes (No Binge group; n = 87). Women in the Binge group endorsed significantly higher ED, PTSD, and depression symptoms at baseline than those in the No Binge group. Although all participants showed significant reductions in PTSD symptoms and improvements in abstinence rates during the study period, the improvements for the Binge group were significantly lower. These findings suggest that a subgroup of women with co-occurring PTSD and SUDs, who endorsed binge ED symptoms, responded differently to SUD/PTSD group treatment. Identification of ED symptoms among treatment-seeking women with SUDs may be an important element in tailoring interventions and enhancing treatment outcomes. Cohen LR, Greenfield SF, Gordon S, Killeen T, Jiang H, Zhang Y, Hien D. Am J Addict. 2010; 19(3): 245-251.
The Role of Alcohol Misuse In PTSD Outcomes For Women In Community Treatment: A Secondary Analysis of NIDA's Women and Trauma Study (CTN-0015)
Individuals with comorbid substance use and posttraumatic stress disorder may differentially benefit from integrated trauma-focused interventions based on specific presenting characteristics such as substance use type and PTSD severity. The current study is a secondary analysis of a NIDA Clinical Trials Network study exploring the effectiveness of two interventions for women with comorbid PTSD and substance use disorders. Generalized estimating equations were used to examine the association of baseline alcohol misuse with PTSD outcome measures over time for all randomized participants. Women entering treatment with baseline alcohol misuse had higher Post Traumatic Stress Disorder Symptom Scale (PSS-SR) total scores (t=2.43, p<.05), cluster C (avoidance/numbing) scores (p<.01), and cluster D (hyper-arousal) scores (p<.05). For women with alcohol misuse, after treatment week 1, PSS-SR scores were significantly lower in the Seeking Safety intervention during treatment (p<.05) and follow-up (p<.05) compared to those in the health education intervention. Alcohol misusers in the Seeking Safety group who had higher baseline hyper-arousal severity improved more quickly than those with lower baseline hyper-arousal severity during treatment (p<.05). Hien DA, Campbell AN, Ruglass LM, Hu MC, Killeen T. Drug Alcohol Depend. 2010 May 25. [Epub ahead of print].
Gender Differences in the Rates and Correlates of HIV Risk Behaviors Among Drug Abusers
This study examined gender differences in the rates and correlates of HIV risk behaviors among 1,429 clients participating in multi-site trials throughout the United States between 2001 and 2005 as part of the National Institute on Drug Abuse-funded Clinical Trials Network. Certain risk factors differed between men and women. Women had overall higher sexual risk than men, due to multiple partners and unprotected sex. However men were more likely to inject drugs than women. Greater alcohol use and psychiatric severity were associated with higher risk behaviors for women, while impaired social relations were associated with decreased risk for men. Specific risk factors were differentially predictive of HIV risk behaviors for women and men, highlighting the need for gender-specific risk-reduction interventions. Brooks A, Meade CS, Potter JS, Lokhnygina Y, Calsyn DA, Greenfield SF. Subst Use Misuse. 2010 Jun 10. [Epub ahead of print].
Alterations In Brain Structure and Functional Connectivity In Prescription Opioid-Dependent Patients
A dramatic increase in the use and dependence of prescription opioids has occurred within the last 10 years. The consequences of long-term prescription opioid use and dependence on the brain are largely unknown, and any speculation is inferred from heroin and methadone studies. Thus, no data have directly demonstrated the effects of prescription opioid use on brain structure and function in humans. To pursue this issue, investigators used structural magnetic resonance imaging, diffusion tensor imaging and resting-state functional magnetic resonance imaging in a highly enriched group of prescription opioid-dependent patients [(n=10); from a larger study on prescription opioid dependent patients (n=133)] and matched healthy individuals (n=10) to characterize possible brain alterations that may be caused by long-term prescription opioid use. In comparison to control subjects, individuals with opioid dependence displayed bilateral volumetric loss in the amygdala. Prescription opioid-dependent subjects had significantly decreased anisotropy in axonal pathways specific to the amygdala (i.e. stria terminalis, ventral amygdalofugal pathway and uncinate fasciculus) as well as the internal and external capsules. In the patient group, significant decreases in functional connectivity were observed for seed regions that included the anterior insula, nucleus accumbens and amygdala subdivisions. Correlation analyses revealed that longer duration of prescription opioid exposure was associated with greater changes in functional connectivity. Finally, changes in amygdala functional connectivity were observed to have a significant dependence on amygdala volume and white matter anisotropy of efferent and afferent pathways of the amygdala. These findings suggest that prescription opioid dependence is associated with structural and functional changes in brain regions implicated in the regulation of affect and impulse control, as well as in reward and motivational functions. These results may have implications for uncovering the effects of long-term prescription opioid use on brain structure and function. Upadhyay J, Maleki N, Potter J, Elman I, Rudrauf D, Knudsen J, Wallin D, Pendse G, McDonald L, Griffin M, Anderson J, Nutile L, Renshaw P, Weiss R, Becerra L, Borsook D. Brain. 2010; 133(Pt 7): 2098-2114. Epub 2010 Jun 16.
Comparison of Opiate-Primary Treatment Seekers With and Without Alcohol Use Disorder
Many persons seeking opiate treatment present with complex clinical challenges, which may be exacerbated by alcohol misuse. This report details secondary data analyses aggregating treatment-seeking samples across 10 National Institute on Drug Abuse (NIDA) Clinical Trials Network treatment trials to examine alcohol-related characteristics of opiate-primary (OP) clients and compare broad pretreatment characteristics of those with and without an alcohol use disorder (AUD). Analysis of this aggregate OP client sample (n = 1,396) indicated that 38% had comorbid AUD and that a history of alcohol treatment episodes and recent alcohol problems were common. Further, comparisons of OP clients with and without AUD revealed the former were more likely to have had a history of pervasive difficulties in psychosocial functioning. Findings suggest the need for detection of and intervention for alcohol misuse at the outset of opiate treatment and support for the practice of availing medical, psychological, case management, and other support services. Hartzler B, Donovan DM, Huang Z. J Subst Abuse Treat. 2010; 39(2): 114-123. Epub 2010 Jul 3.
Substance Abuse Treatment Providers' Involvement In Research Is Associated With Willingness To Use Findings In Practice
Using a national sample (n = 571) of substance abuse treatment providers affiliated with the Clinical Trials Network, investigators examined the contribution of several factors-demographic, attitudes, and involvement in research-toward providers' willingness to use research findings in practice. The sample included medical staff, social workers, psychologists, and counselors. Using a multiple linear regression model, investigators examined the impact of involvement in research and willingness to use research findings in practice. Providers involved in research were more willing to use findings in practice (p < .001). Latino/Latinas were less willing (p < .05). Providers with favorable attitudes toward evidence-based practices and whose agencies supported professional growth were more willing to use findings (p < .01). Involvement in research may enhance providers' willingness to use findings in practice and improve quality of services. Pinto RM, Yu G, Spector AY, Gorroochurn P, McCarty D. J Subst Abuse Treat. 2010; 39(2): 188-194.
Reducing HIV-Related Risk Behaviors Among Injection Drug Users in Residential Detoxification
This study of 632 drug injectors enrolled in eight residential detoxification centers within the National Drug Abuse Treatment Clinical Trials Network tested three interventions to reduce drug and sex risk behaviors. Participants were randomized to: (a) a two-session, HIV/HCV counseling and education (C&E) model added to treatment as usual (TAU), (b) a one-session, therapeutic alliance (TA) intervention conducted by outpatient counselors to facilitate treatment entry plus TAU, or (c) TAU. Significant reductions in drug and sex risk behaviors occurred for all three conditions over a 6-month follow-up period. C&E participants reported significantly greater rates of attending an HIV testing appointment, but this was not associated with better risk reduction outcomes. Reporting treatment participation within 2 months after detoxification and self-efficacy to practice safer injection behavior predicted reductions in injection risk behaviors. Findings indicate that participation in detoxification was followed by significant decreases in drug injection and risk behaviors for up to 6-months; interventions added to standard treatment offered no improvement in risk behavior outcomes. Booth RE, Campbell BK, Mikulich-Gilbertson SK, J Tillotson C, Choi D, Robinson J, Calsyn DA, Mandler RN, Jenkins LM, Thompson LL, Dempsey CL, Liepman MR, McCarty D. AIDS Behav. 2010 Jul 21. [Epub ahead of print]