Exercise in Methamphetamine Use Disorder Upregulation and Neural Function

Early Phase 1

Completed

• Conditions: Methamphetamine Abuse
• Interventions: Behavioral: EX; Behavioral: CON

• Registration Number: NCT03709667
• Lead Sponsor: University of California, Los Angeles

Brief Summary

The purpose of this research study is to determine the effects of an exercise intervention and health-education program on brain dopamine receptors and on cognitive functions that have been linked to these receptors.

Detailed Description

After completing baseline assessments within 2 wks after admission, participants will be randomized to one of two interventions: Exercise (EX, active intervention), consisting of 3x-weekly 50-min aerobic + resistance-training sessions for 8 wk; Health Education (control intervention, CON), consisting of 50-min health education sessions 3x-weekly for 8 wk. Participants will undergo positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scans while performing the stop signal task (SST) and the reversal learning task (RLT) (cognitive computer tasks) at baseline and after completing the 8-wk protocol.

Study Timeline

• Study First Submitted: 2018-07-12
• Study First Submitted QC: 2018-10-12
• Study First Posted: 2018-10-17
• Study Start: 2019-06-26
• Primary Completion: 2023-08-30
• Study Completion: 2023-08-30
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-06
• Last Update Posted: 2024-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 113

Inclusion Criteria

1. Language: Participants must be fluent in English, as demonstrated by verbal skills sufficient to participate in a conversation, including the ability to ask and answer questions at a level that assures adequate understanding of the study. A comprehension quiz will be administered.
2. Age 18-65 years
3. Meets Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for moderate to severe stimulant use disorder assessed by MINI.
4. Vital Signs: Within the clinically acceptable normal range (e.g., resting pulse 50 to 99/min, blood pressure between 85-150 mm Hg systolic and 45-90 mm Hg diastolic.
5. Labs: hematology and chemistry laboratory test results within normal (+/- 10%) limits.
6. Right handed.

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Exclusion Criteria

1. Neurological disease: history of seizure disorder, brain injury with loss of consciousness > 30 min, or other neurological disorder that would interfere with informed consent, data interpretation or participant safety.
2. Musculoskeletal disease that would prevent participation in exercise.
3. Current psychotic disorder assessed by the MINI.
4. Current suicidal ideation/plan, assessed by the Patient Health Questionnaire-9.
5. Heart disease: Hypertension or unstable pulmonary or cardiovascular disease that would interfere with participation in the EX regimen
6. Evidence of untreated or unstable medical illness, including endocrine, autoimmune, renal, hepatic, or active infectious disease, which might compromise safe participation (HIV+ participants must be receiving a stable regimen of antiretroviral medication throughout the course of the study).
7. Pregnancy [Women must provide negative pregnancy urine tests before study entry].
8. Asthma or use of theophylline, α- and β-adrenergic agonists, or other sympathomimetics.
9. Medications: Antihypertensive agents, antidepressants, and antiretroviral medications are prescribed to some clients at Cri-Help. Any participant taking any medication that has direct dopaminergic action (e.g., bupropion, neuroleptics) will be excluded, but other chronic medications such as selective serotonin reuptake inhibitors will be allowed. Any participant taking a medication chronically must maintain a stable dose throughout the study; antiretrovirals and antidepressants must be initiated at least 1 week before baseline scan.
10. Radiation Exposure: Participants who have participated in any other research study involving exposure to ionizing radiation in the past year if the total cumulative dose from the past research studies and the current research study would exceed the limits described by the FDA in 21 Code of Federal Regulations 361.1. Specifically, the total annual cumulative dose to the body, active blood-forming organs, lens of the eye and gonads must remain below 5 rems and the total annual cumulative dose to all other organs must remain below 15 rems. Potential participants who have had exposure to ionizing radiation in the past year cannot be allowed to participate if the investigators are unable to obtain proper documentation quantifying the amount of past exposure.
11. Metal devices: (e.g., pacemaker, infusion pump, aneurysm clip, prosthesis, plate) in the body.Presence of such a device could interfere with scan acquisition or pose a potential risk during MRI. [A participant who has an implanted device can enroll with documentation that the device is MRI-compatible.
12. Claustrophobia: Subjects will be questioned about their potential discomfort with enclosed spaces, such as an MRI scanner. Subjects reporting problems with enclosed spaces will be excluded.
13. Any other condition that would compromise safe participation, determined by the study physician.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EX	EX	Participants in this arm of the study will be randomized in to the exercise intervention.
CON	CON	The control condition is a health-education intervention.

Primary Outcome Measures

Name	Time	Method
Striatal D2/3 Binding Potential (BPND) Upregulation	8 weeks	Dopamine D2-type receptor binding potential in the striatum measured with positron emission tomography scanning measured at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment.

Secondary Outcome Measures

Name	Time	Method
Inhibitory control - reversal learning	8 weeks	A reversal learning task will be used to assess inhibitory control at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment.
Reward-based decision-making	8 weeks	A monetary delay-discounting task/questionnaires and the Balloon Analogue Risk task will be used to assess reward-based decision-making at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment. The primary outcome measures include the number of balloon pumps and earnings, with more pumps and earnings reflecting greater risk.
Resting state functional connectivity	8 weeks	Striatum resting state functional connectivity will be measured with a functional magnetic resonance imaging scan at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment.
Sustained attention	8 weeks	The Continuous Performance Task will be used to assess sustained attention at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment. The following outcome variables will be assessed: Correct Detection: Number of responses to the target stimulus. Reaction times: Length of time between stimulus presentation and response. Omission errors: Number of target presentations with no response. Commission errors: Number of responses without target stimulus presentation.; High omission rates reflect impaired attention, higher correct detections reflect improved attention.
Declarative memory	8 weeks	The Rey Auditory Verbal Learning Test will be used to assess declarative memory at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment. The number of words correctly recalled will be recorded before and after a 20 minute delay, as well as the number of intrusions. The corresponding Z score and percentile of each participant's responses will be calculated.
Task-based brain activity (functional magnetic resonance imaging - stop signal	8 weeks	Performance on a cognitive task the (Stop Signal Task), will be assessed during a functional magnetic resonance imaging scan at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment.
Selective attention	8 weeks	The Stroop Task will be used to assess working memory at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment. The number of words, colors, and number of color words within a set time will be measured, as well as the number of errors. Larger amounts of errors reflect worse selective attention, whereas higher numbers of words, colors, and number of color words completed reflect better selective attention.
Inhibitory control - stop signal task	8 weeks	The Stop-signal task will be used to assess inhibitory control at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment.
Task-based brain activity (functional magnetic resonance imaging) - balloon analog risk	8 weeks	Performance on a cognitive task (the Balloon Analog Risk Task) will be assessed during a functional magnetic resonance imaging scan at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment.
Decision making under risk and ambiguity	8 weeks	A task involving decision making under during differing types of risk and ambiguity will be used to determine decision making under risk and ambiguity at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment. The Risk and Ambiguity Task measures tolerance for risk under conditions of known risk (alpha) and unknown risk (beta).
Loss Aversion	8 weeks	A computer task and written questionnaire assessing loss preferences will be used to assess loss aversion at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment.
Working memory	8 weeks	The Sternberg Spatial Task will be used to assess working memory at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment. The number of correct responses will be measured, with higher amounts of correct responses reflecting better working memory.
Motor Function	8 weeks	A finger tapping test will be to assess motor function at baseline prior to exercise (EX) and after 8 weeks of EX (vs. CON) treatment. The number of finger taps in 10 seconds will be recorded three times per hand, and averaged to create the primary outcome measure reflecting motor function.

Trial Locations

Locations (1)

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States