Stimulant Reduction Intervention using Dosed Exercise (STRIDE) - CTN 0037: Study protocol for a randomized controlled trial

Trials Stimulant Reduction Intervention using Dosed Exercise (STRIDE) - CTN 0037: Study protocol for a randomized controlled trial Madhukar H Trivedi 0 Tracy L Greer 0 Bruce D Grannemann 0 Timothy S Church Eugene Somoza Steven N Blair Jose Szapocznik Mark Stoutenberg Chad Rethorst 0 Diane Warden 0 Kolette M Ring 0 Robrina Walker 0 David W Morris 0 Andrzej S Kosinski Tiffany Kyle Bess Marcus Becca Crowell Neal Oden Edward Nunes 0 The University of Texas Southwestern Medical Center at Dallas , 5323 Harry Hines Blvd., Dallas, Texas, 75390-9119 , USA Background: There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study. Methods/Design: STRIDE is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. This study will evaluate individuals diagnosed with stimulant abuse or dependence who are receiving treatment in a residential setting. Three hundred and thirty eligible and interested participants who provide informed consent will be randomized to one of two treatment arms: Vigorous Intensity High Dose Exercise Augmentation (DEI) or Health Education Intervention Augmentation (HEI). Both groups will receive TAU (i.e., usual care). The treatment arms are structured such that the quantity of visits is similar to allow for equivalent contact between groups. In both arms, participants will begin with supervised sessions 3 times per week during the 12-week acute phase of the study. Supervised sessions will be conducted as one-on-one (i.e., individual) sessions, although other participants may be exercising at the same time. Following the 12-week acute phase, participants will begin a 6-month continuation phase during which time they will attend one weekly supervised DEI or HEI session. stimulant abuse; stimulant dependence; exercise; health education; behavioral intervention - Background There is a need for novel approaches to the treatment of stimulant use disorders. Stimulant use disorders are chronic, relapsing illnesses with few highly efficacious treatments [1]. In control conditions (Treatment as Usual; TAU) for substance use disorders, typically only about 13% of participants achieve abstinence [1]. Abstinence rates for treatments designed to augment TAU vary widely - ranging from 14-60%[2-5] - depending on the outcome variable and primary endpoint selected. Currently, the best treatments for cocaine and other stimulant use disorders are behavioral treatments that combine cognitive behavioral therapy (CBT) with contingency management [1,6]. However, it is clear that new treatments are still needed for stimulant abuse and dependence. Exercise is a promising new treatment option for stimulant abuse and dependence. Randomized controlled trials examining exercise to improve outcomes in smoking cessation provide some of the most convincing support for investigating the use of exercise (and most frequently, vigorous intensity exercise) to improve outcomes in stimulant abuse [7-11]. While randomized controlled trials in patients abusing substances other than tobacco or alcohol are not yet available, some studies report benefits such as increased abstinence and reduced substance use that are associated with the use of exercise [12-14]. Furthermore, in a post hoc analysis of data from 187 participants in two randomized trials evaluating contingency management for the treatment of substance abuse disorders [15,16], participants who reported engaging in exercise-related activities had an increased length of abstinence [17]. In a recent pilot study of moderate-intensity aerobic exercise added to treatment for 16 individuals with substance dependence, percent days abstinent significantly increased from baseline, and 66.7% of the sample had been continuously abstinent at the end of a 12-week intervention [18]. Exercise may also provide additional health benefits and functional improvements for stimulant users. Exercise has been shown to reduce depression and anxiety during alcohol treatment [19-21], as well as smoking cessation treatment [22-24]. Exercise is also associated with improved quality of life [25] and sleep [26], both of which are disrupted by stimulant use even after abstinence is achieved [27,28]. In addition, concern about weight gain following cessation of abused substances may increase risk of substance use relapse [29-31], and regular exercise may prevent or reduce post cessation weight gain. Furthermore, Greenwood et al. [32] has demonstrated improvements in hippocampal-dependent contextual learning and memory in rats with exercise. Similar results have been found for exercise-induced hippocampal neurogenesis and improvements in spatial memory in rats and mice [33-35]. Since substance abuse has been associated with memory impairments that are influenced by hippocampal function [36], exercise may be associated with improved memory for these individuals. Exercise may improve outcomes through any of several possible mechanisms. Exercise is likely to impact the underlying biology of addicted persons, as well as act as a behavioral treatment intervention. Summarizing studies of the effect of exercise on neurotransmitters [37] conclude that exercise results in changes in synthesis and metabolism within central dopaminergic, noradrenergic, and serotonergic systems, all of which are implicated in addiction. Additional biological effects of exercise may include decreased reactivity to stress [38] and decreased use of substances as a way of coping with stress [39]. Exercise-induced improvements in self-efficacy [40,41] may be another mechanism for improving outcomes. It has also been suggested that exercise may be a distraction [42], allowing attention to be diverted from urges to use substances [43] or a positive lifestyle change that can substitute for use of substances [44,45]. The current paper provides a description of the design of the Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study, a multisite randomiz (...truncated)