Search the Library

Abstract: Background and aims: Sleep disruptions increase the risk of substance misuse. Substance use-especially stimulants-can increase acute and chronic sleep dysfunction. This study aimed to estimate the associations between sleep disturbance and stimulant use over time among participants with stimulant use disorder (StUD). Design: In this secondary analysis, a Random Intercept Cross-Lagged Panel Model (RI-CLPM) was used to assess sleep disturbance and stimulant use over 8 weeks among participants with StUD. Setting: United States of America. Participants: The analysis included 793 participants with StUD enrolled across 3 randomized controlled trials in the National Institute on Drug Abuse’s Clinical Trials Network (CTN): CTN-0037, CTN-0048 and CTN-0068. Measurements: Self-reported sleep disturbance was harmonized as a binary indicator across trial measures at each week. Stimulant use days per week were captured by Timeline Follow Back. Baseline covariates included age, sex, race/ethnicity, employment status, presence of depressive symptoms, any psychiatric history, treatment arm and trial. Findings: Sleep disturbance was associated with a higher average number of stimulant use days the following week [β = 0.15, 95% confidence interval (CI) = 0.09, 0.22, P < 0.001], and greater stimulant use was linked to increased odds of subsequent sleep disturbance (odds ratio = 1.20, 95% CI = 1.14, 1.26, P < 0.001). Conclusions: Higher-than-usual stimulant use appears to be associated with increased likelihood of sleep disturbance the following week, and vice versa. Related protocols: CTN-0037, CTN-0048, CTN-0068

Abstract:

High levels of missing outcome data for biologically confirmed substance use (BCSU) threaten the validity of substance use disorder (SUD) clinical trials. Underlying attributes of clinical trials could explain BCSU missingness and identify targets for improved trial design.

We reviewed 21 clinical trials funded by the NIDA National Drug Abuse Treatment Clinical Trials Network (CTN) and published from 2005 to 2018 that examined pharmacologic and psychosocial interventions for SUD. We used configurational analysis-a Boolean algebra approach that identifies an attribute or combination of attributes predictive of an outcome-to identify trial design features and participant characteristics associated with high levels of BCSU missingness. Associations were identified by configuration complexity, consistency, coverage, and robustness. We limited results using a consistency threshold of 0.75 and summarized model fit using the product of consistency and coverage.

For trial design features, the final solution consisted of two pathways: psychosocial treatment as a trial intervention OR larger trial arm size (complexity=2, consistency=0.79, coverage=0.93, robustness score=0.71). For participant characteristics, the final solution consisted of two pathways: interventions targeting individuals with poly- or nonspecific substance use OR younger age (complexity=2, consistency=0.75, coverage=0.86, robustness score=1.00).

Conclusions: Psychosocial treatments, larger trial arm size, interventions targeting individuals with poly- or nonspecific substance use, and younger age among trial participants were predictive of missing BCSU data in SUD clinical trials. Interventions to mitigate missing data that focus on these attributes may reduce threats to validity and improve utility of SUD clinical trials.

Related protocols: CTN-0002, CTN-0003, CTN-0004, CTN-0006, CTN-0007, CTN-0009. CTN-0013, CTN-0014, CTN-0015, CTN-0017, CTN-0021, CTN-0029, CTN-0030, CTN-0031, CTN-0037, CTN-0044, CTN-0046, CTN-0048, CTN-0051, CTN-0053

Abstract:

Suicide is the tenth leading cause of death in the United States and continues to be a major public health concern. Suicide risk is highly prevalent among individuals with co-occurring substance use disorders (SUD) and mental health disorders, making them more prone to adverse substance use related outcomes including overdose. Identifying individuals with SUD who are suicidal, and therefore potentially most at risk of overdose, is an important step to address the synergistic epidemics of suicides and overdose fatalities in the United States. The current study assesses whether patterns of suicidality endorsement can indicate risk for substance use and overdose.

Latent class analysis (LCA) was used to assess patterns of item level responses to the Concise Health Risk Tracking Self-Report (CHRT-SR), which measures thoughts and feelings associated with suicidal propensity. We used data from 2,541 participants with SUD who were enrolled across 8 randomized clinical trials in the National Drug Abuse Treatment Clinical Trials Network from 2012 to 2021 (CTN-0037, -0049, -0051, -0053, -0054, -0064, -0067, -0068). Characteristics of individuals in each class were assessed, and multivariable logistic regression was performed to examine class membership as a predictor of overdose. LCA was also used to analyze predictors of substance use days.

Three classes were identified and discussed: Class (1) Minimal Suicidality, with low probabilities of endorsing each CHRT-SR construct; Class (2) Moderate Suicidality, with high probabilities of endorsing pessimism, helplessness, and lack of social support, but minimal endorsement of despair or suicidal thoughts; and Class (3) High Suicidality with high probabilities of endorsing all constructs. Individuals in the High Suicidality class comprise the highest proportions of males, Black/African American individuals, and those with a psychiatric history and baseline depression, as compared with the other two classes. Regression analysis revealed that those in the High Suicidality class are more likely to overdose as compared to those in the Minimal Suicidality class (p = 0.04).

Conclusions: Suicidality is an essential factor to consider when building strategies to screen, identify, and address individuals at risk for overdose. The integration of detailed suicide assessment and suicide risk reduction is a potential solution to help prevent suicide and overdose among people with SUD.

Related protocols: CTN-0037, CTN-0049, CTN-0051, CTN-0053, CTN-0054, CTN-0064, CTN-0067, CTN-0068

Abstract:

Increasing rates of overdose and overdose deaths are a significant public health problem. Research has examined co-occurring mental health conditions, including suicidality, as a risk factor for intentional and unintentional overdose among individuals with substance use disorder (SUD). However, this research has been limited to single site studies of self-reported outcomes.

The current research evaluated suicidality as a predictor of overdose events in 2541 participants who use substances enrolled across eight multi-site clinical trials completed within the National Drug Abuse Treatment Clinical Trials Network between 2012 to 2021 (CTN-0037, -0049, -0051, -0053, -0054, -0064, -0067, and -0068). The trials assessed baseline suicidality with the Concise Health Risk Tracking Self-Report (CHRT-SR). Overdose events were determined by reports of adverse events, cause of death, or hospitalization due to substance overdose, and verified through a rigorous adjudication process. Multivariate logistic regression was performed to assess continuous CHRT-SR score as a predictor of overdose, controlling for covariates.

CHRT-SR score was associated with overdose events (p=0.03) during the trial; the likelihood of overdose increased as continuous CHRT score increased (OR 1.02). Participants with lifetime heroin use were more likely to overdose (OR 3.08).

Conclusions: Response to the marked rise in overdose deaths should integrate suicide risk reduction as part of prevention strategies.

Related protocols: CTN-0037, CTN-0049, CTN-0051, CTN-0053, CTN-0054, CTN-0064, CTN-0067, CTN-0068

Abstract:

Exercise is a promising treatment for stimulant use disorder. However, efficacy has not been clearly demonstrated in a general stimulant using population where response to exercise is expected to be heterogeneous. Thus, examination of response heterogeneity to identify subgroups for whom exercise is either clearly indicated or not indicated is of considerable interest as findings will support more effective tailoring of patient treatments in practice and guide future research in stimulant use disorder. A secondary analysis of the Stimulant Reduction Intervention using Dosed Exercise (STRIDE) randomized controlled trial of 302 stimulant using or dependent participants was conducted to identify baseline clinical and demographic characteristics associated with differential response between participants in the exercise and health education control groups. Characteristics (i.e., moderators of treatment response) were identified using an established Best Approximating Modeling (BAM) method. Six moderators of treatment response were identified: Quick Inventory of Depressive Symptomatology – Clinician (QIDS-C) rated total score, exercise test maximum systolic blood pressure, number of lifetime drug treatments, Stimulant Craving Questionnaire (STCQ) total score, Addiction Severity Index (ASI) Family subscale score, and Cognitive and Physical Functioning Questionnaire (CPFQ) total score. For all moderators, the odds ratio of response to exercise vs. health education ranged from 0.32 to 2.52 or more depending on the level of the moderator.

Conclusions: These results demonstrate that it is possible to identify pre-treatment patient characteristics that predict statistically and clinically meaningful differential treatment response to exercise.

Related protocols: CTN-0037

Abstract:

Exercise may be beneficial for individuals in substance use disorder (SUD) treatment given the higher rates of both medical and psychiatric comorbidity, namely mood and anxiety disorders, compared to the general population. Gender and/or racial/ethnic differences in health benefits and response to prescribed exercise have been reported and may have implications for designing exercise interventions in SUD programs.

Using data from the NIDA Clinical Trials Network Stimulant Reduction Intervention using Dosed Exercise (STRIDE) trial, CTN-0037, gender differences and stimulant withdrawal severity across time were analyzed using linear mixed effects models.

The analysis found that males completed significantly more exercise sessions than females and were more adherent to the prescribed exercise dose of 12 Kcal/Kg/Week. Controlling for age, race/ethnicity, treatment group and stimulant withdrawal severity, there was a significant gender by time interaction for body mass index (BMI), waist circumferences, and heart rate measured prior to exercise sessions. For females, body mass index and waist circumference increased over time, while for males, BMI and waist circumference stayed unchanged or slightly decreased with time. Heart rate over time significantly increased for females at a higher rate than in males. Stimulant withdrawal severity was similar in males and females at baseline but males exhibited a significant decrease over time while females did not. Although baseline differences were observed, there were no time by race/ethnicity differences in physiologic responses.

Conclusions: Gender differences in response to exercise may have implications for developing gender specific exercise interventions in SUD programs.

Related protocols: CTN-0037

Abstract:

The National Drug Abuse Treatment Clinical Trials Network (CTN) was initiated by the National Institute on Drug Abuse (NIDA) in 2000 with the aim of improving substance use treatment and reducing the time between the discovery of effective treatments and their implementation into clinical practice. While initial trials were conducted almost exclusively in specialty addiction treatment settings, the CTN began evolving strategically in 2010 to conduct research in general medical settings, including healthcare systems, primary care settings, emergency departments, and pharmacies, to broaden impact. The advantages of a research network like the CTN is not only the collective content expertise that investigators contribute to the network, but the collective experience gained by conducting studies in the network and then applying those lessons to future studies.

This study aimed to summarize trial implementation challenges encountered, and the process by which solutions were identified and implemented, within one of the last early-phase CTN Stage II behavioral intervention studies conducted in a specialty addiction treatment setting, CTN-0037, the Stimulant Reduction Intervention Using Dosed Exercise (STRIDE) trial.

Issues encountered during study implementation are categorized into four major areas, described in terms useful to future study teams: 1) study team infrastructure challenges, 2) participant- and site- level challenges, 3) intervention-related challenges, and 4) longitudinal study design challenges. Potential consequences of identified problems and the solutions developed to manage these problems are discussed within the context of these four areas. The authors propose how to extend these implementation lessons and apply them in other healthcare settings to expand the CTN.

Conclusions: Effective study management allows for flexible, collaborative solutions to expected and unexpected obstacles to study success. Implementation strategies derived from the first 15 to 20 years of CTN studies are a result of working with providers and participants, and the ongoing collaboration among CTN investigators and network staff. Timely identification and response to problems during study implementation are critical to the success of a trial, regardless of its design. We believe a collaborative approach to identifying and responding to study implementation challenges will increase the likelihood of successful adoption of relevant, efficacious interventions. As the CTN continues to expand, the wealth of successful trial implementation strategies developed during the first 20 years of the CTN need to be applied and adapted to studies in broader network settings, and considered in conjunction with more formalized implementation science processes that are currently available.

Related protocols: CTN-0037

Abstract:

This study aimed to assess the validity of the psychiatric problems subscale of the Addiction Severity Index (ASI-psych) to ascertain psychiatric comorbidity among individuals participating in randomized controlled trials (RCTs) of substance use disorder (SUD) treatments.

The ASI-psych score among 1,660 RCT participants of National Institute of Drug Abuse Clinical Trials Network studies was compared against diagnosis of any serious mental disorder based on the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (SCID) or Mini-International Neuropsychiatric Interview (MINI). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for detecting any serious mental disorders were estimated by the receiver operating characteristic (ROC) analysis.

Based on the overall sample, the AUC score for any serious mental disorder was 0.72 (95% confidence interval [CI], [0.69, 0.75]) with the optimal ASI-psych score of 24.6. There was no statistically significant difference in AUCs based on the SCID and MINI or by target drugs of RCTs.

Conclusions: Results support the utility of the ASI in screening for psychiatric comorbidity among patients receiving SUD treatments in RCT settings.

Related protocols: CTN-0005, CTN-0037

Abstract:

The aim of this study was to examine the impact of vigorous intensity, high dose exercise (DEI) on cannabis use among stimulant users compared to a health education intervention (HEI) using data from the Stimulant Reduction Intervention using Dosed Exercise NIDA Clinical Trials Network study (CTN-0037).

Adults (N=302) enrolled in the STRIDE randomized clinical trial were randomized to either the DEI or the HEI. Interventions included supervised sessions three times a week during the Acute phase (12 weeks) and once a week during the Follow-up phase (6 months). Cannabis use was measured at each assessment via Timeline Follow Back and urine drug screens. Cannabis use was compared between the groups during the Acute and Follow-up phases using both the intent-to-treat sample and a complier average causal effects (CACE) analysis.

Approximately 43% of the sample reported cannabis use at baseline. The difference in cannabis use between the DEI and HEI groups during the Acute phase was not significant. During the Follow-up phase, the days of cannabis use was significantly lower among those in the DEI group (1.20 days) compared to the HEI gruop (2.15 days; p=0.04).

Conclusions: Results suggest that there were no significant short-term differences in cannabis use between the two groups. However, there were long-term differences between participants in the DEI and HEI groups. Specifically, those who adhered to the exercise intervention, vigorous intensity, high-dose exercise resulted in less cannabis use at follow-up. Further study on the long-term impact of exercise as a treatment to reduce cannabis use should be considered.

Related protocols: CTN-0037

Abstract:

The purpose of this study was to estimate obesity prevalence among drug-dependent individuals and to compare prevalence across different types of drug dependence.

1596 opioid- and/or stimulant-dependent participants were extracted from six clinical trials within the National Drug Abuse Treatment Clinical Trials Network of the National Institute on Drug Abuse (NIDA CTN) to estimate obesity prevalence among drug-dependent users. Age-, sex-, and race-matched National Health and Nutrition Examination Survey (NHANES) samples were used as a general population reference. Standardized prevalence ratios (SPRs) were calculated to compare the CTN sample to NHANES as well as to compare within the CTN sample. Logistic regression estimated associations between the type of drug dependence and obesity.

The standardized obesity prevalence among the drug-dependent CTN trial participants was 67% of expected for age-, sex- and race-matched NIHANES participants (SPR = 0.67, 95% CI: 0.60-0.74). Obesity was least prevalent among opioid-dependent-only participants (SPR = 0.36, 95% CI: 0.27-0.46 compared to the NHANES, and SPR = 0.33, 95% CI: 0.23-0.46 compared to the stimulant-dependent-only participants). Compared to stimulant-dependent-only users (p < 0.0001), the odds of obesity were 67% lower among opioid-dependent-only users (adjusted odds ratio [AOR] = 0.33, 95% CI: 0.23-0.46) and 33% lower among opioid and stimulant-co-dependent users (AOR = 0.67, 95%CI: 0.49-0.90) after controlling for age, sex, race, education and employment pattern.

Conclusions: The prevalence of obesity among drug-dependent clinical trial participants was lower than the general population, and lowest among opioid-dependent-only users, suggesting an inverse relationship between obesity prevalence and drug dependence, most notable among opioid-dependent-only users.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0037, CTN-0046, CTN-0048

Abstract:

Exercise is a promising treatment for substance use disorders, yet an intention-to-treat analysis of a large, multi-site study found no reduction in stimulant use for exercise versus health education. Exercise adherence was sub-optimal, therefore secondary post-hoc complier average causal effects (CACE) analysis was conducted to determine the potential effectiveness of adequately dosed exercise.

The STimulant use Reduction Intervention using Dosed Exercise (STRIDE) study was a randomized controlled trial comparing a 12 kcal/kg/week (KKW) exercise dose versus a health education control conducted at 9 residential substance use treatment settings across the U.S. that are affiliated with the National Drug Abuse Treatment Clinical Trials Network. Participants were sedentary but medically approved for exercise, used stimulants within 30 days prior to study entry, and received a DSM-IV stimulant abuse or dependence diagnosis within the past year. A CACE analysis adjusted to include only participants with a minimum threshold of adherence (at least 8.3 KKW) and using a negative-binomial hurdle model focused on 218 participants who were 36.2% female, mean age 39.4 years (SD=11.1), and averaged 13 (SD=9.2) stimulant use days in the 30 days before residential treatment. The outcome was days of stimulant use as assessed by the self-report TimeLine Follow Back and urine drug screen results.

The CACE-adjusted analysis found a significantly lower probability of relapse to stimulant use in the exercise group versus the health education group (41% vs. 55.7%, p<.01) and significantly lower days of stimulant use among those who relapsed (5 days vs. 9.9 days, p<.01).

Conclusions: The CACE efficacy analysis was conducted for the STRIDE study to account for exercise dose in the evaluation of exercise as a potential treatment for stimulant use disorders. This analysis demonstrated statistically significant differences for the probability of stimulant use, such that those who would achieve an adequate exercise dose (defined to be an average of 8.3 KKW or more) have an estimated lower probability of relapsing to any stimulant use. Analyses also demonstrated that, even among those who relapsed, the amount of estimated stimulant use was significantly less among those who would achieve an adequate exercise dose. Together, these results suggest a beneficial effect of exercise in the treatment of stimulant abuse. Further research is warranted to develop strategies for exercise adherence that can ensure achievement of an exercise dose sufficient to produce a significant treatment effect.

Related protocols: CTN-0037

Abstract:

Stimulant use disorders are both common and associated with suicidal ideation and attempts. The psychometric properties of the 12-item Concise Health Risk Tracking Scale Self-Report (CHRT-SR), a measure that was created to assess suicidal thinking and several factors associated with a propensity to act, has been established in persons with mood disorders. This is a secondary analysis to assess the CHRT-SR in 302 stimulant abusing patients who had participated in a clinical trial (NIDA Clinical Trials Network protocol CTN-0037, Stimulant Reduction Intervention Using Dosed Exercise (STRIDE)).

A confirmatory factor analysis (CFA) was conducted to assess the factor validity of the 12-item CHRT-SR model with a second-order Propensity factor. The CHRT-SR total score and 2 factor scores (Propensity and Suicidal Thoughts) demonstrated acceptable internal consistency and test-retest reliabilities. These two subscales and the total score were modestly but significantly associated with measures of depression and life satisfaction, demonstrating construct validity. Two additional items assessing Impulsivity were also analyzed, and demonstrated acceptable internal consistency, test-retest reliability, and construct validity.

Conclusions: The CHRT-SR appears to be a reliable and valid tool to assess suicidality in persons with stimulant use disorder. The value of a brief self-report measure of suicidal risk with promising psychometric properties has strong implications for practice and for clinical trials. The CHRT-SR is straightforward, requiring minimal clinician time to train and administer, and offers particular utility as a simple and quick assessment of helplessness and pessimism, symptoms common among people with chronic stimulant use, a population who should be closely monitored for suicide.

Related protocols: CTN-0037

Abstract:

The self-report Concise Associated Symptoms Tracking Scale (CAST-SR) has been validated as a reliable instrument to track symptoms across the domains of irritability, mania, anxiety, panic, and insomnia in depressed outpatients after beginning antidepressant medication. However, its factor structure, validity, and reliability have not yet been tested in other treatment-seeking populations.

This study evaluated the psychometrics of the CAST-SR in a sample of participants in the multisite Stimulant Reduction Intervention Using Dosed Exercise (CTN-0037) trial: individuals with stimulant use disorder receiving aerobic exercise or health education interventions. The CAST-SR loaded only in individuals with primary stimulant use disorders who were prescribed antidepressant medications, not in all individuals with primary stimulant use disorders.

Conclusions: These results demonstrate the factor structure, reliability, and validity of the CAST-SR in a novel population of only individuals with stimulant use disorders receiving both exercise/health education interventions and antidepressant medication. Clinicians treating antidepressant-receiving individuals with comorbid stimulant use disorders may use the CAST-SR to examine changes in symptoms of anxiety, insomnia, irritability, and panic throughout treatment, thereby optimizing treatment outcomes.

Related protocols: CTN-0037

Abstract:

Relatively little has been reported about the physical characteristics, such as cardiorespiratory fitness (CRF) and body composition, of stimulant users. Identifying risk factors associated with the physical health of stimulant users is an important public health issue as new treatments should better address the entire range of health concerns experienced by this population.

This study examined cross-sectional data gathered at baseline from the STimulant Reduction Intervention using Dosed Exercise (STRIDE) study, a multi-site randomized clinical trial that examined exercise as an adjunct to treatment as usual for individuals in residential treatment programs (RTPs). Clients were approached after intake to the RTP. Prior to randomization, eligible individuals underwent a comprehensive screening process that included medical screening, where CRF was assessed through a maximal exercise test (time on treadmill), and a series of baseline examinations assessing domains of substance use and mental health.

Data from 295 individuals with recent stimulant use disorders were analyzed. The mean body mass index (BMI) and waist circumference (WC) for all participants was 27.8 +/- 5.7 kg/m² and 93.5 +/- 14.2 cm, respectively, while the mean time on treatment was 13.7 +/- 2.9 min. Few significant associations were observed between CRF, BMI, or WC and substance use and mental health measures.

Conclusions: Stimulant users in this study presented with low CRF levels and would be considered overweight based on their BMI. These individuals would likely benefit from interventions that address both their stimulant use, as well as their physical health.

Related protocols: CTN-0037

Abstract:

The current study examined differences in substance abuse treatment outcomes among racial and ethnic groups enrolled in the Stimulant Reduction Intervention using Dosed Exercise (STRIDE) trial, a multisite randomized clinical trial implemented through the National Institute on Drug Abuse’s (NIDA’s) Clinical Trials Network (CTN). STRIDE aimed to test vigorous exercise as a novel approach to the treatment of stimulant abuse compared to a health education intervention. A hurdle model with a complier average causal effects (CACE) adjustment was used to provide an unbiased estimate of the exercise effect had all participants been adherent to exercise.

Among 214 exercise-adherent participants, we found significantly lower probability of use for Blacks (z= -2.45, p=.014) and significantly lower number of days of use for Whites compared to Hispanics (z= -54.87, p=<.001) and for Whites compared to Blacks (z= -28.54, p=<.001), which suggests that vigorous, regular exercise might improve treatment outcomes given adequate levels of adherence.

Conclusions: The STRIDE study demonstrated that intensive exercise interventions for people with stimulant use disorders, in community-based addiction treatment, are feasible. Examining race/ethnicity differences in treatment outcomes using novel approaches is important to understanding disparities and what contributes to success. There is a need for engagement strategies for sustaining Blacks in treatment and recruiting them into treatment earlier in life. Vigorous exercise may benefit racial and ethnic minority populations with stimulant use disorder. Future research should focus on intentional inclusion of race/ethnic groups, early in the study design, to test interventions targeted with a specific focus on what works for certain populations.

Related protocols: CTN-0037