Clinical trial NCT03644927: Exercise Maintenance in Chronic Pain and PTSD
Official title: Neurobiological Mediators of Self-Regulatory and Reward-Based Motivational Predictors of Exercise Maintenance in Chronic Pain and PTSD
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Chronic Low Back Pain
Posttraumatic Stress Disorder
Keywords: Veterans
Cardiopulmonary exercise testing
Exercise maintenance
Neuropeptide Y (NPY)
Exercise-related intrinsic motivation
Exercise Self efficacy
Transtheoretical Model (TTM)
Self-Determination Theory (SDT)
Lead sponsor: Boston University
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2018-08-23
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of the R21 is using an experimental medicine research approach to study whether a chronic, progressive-based exercise program will help Veterans suffering from chronic low back pain (cLBP) and PTSD achieve exercise maintenance, and shared symptom reduction, through neuropeptide Y mediated improvements in putative factors (self-regulation and reward sensitivity) known to improve exercise related self-efficacy and motivation.

Detailed description: This study will compare the effects of a 3-month, individually prescribed progressive exercise training program on: 1) chronic low back pain (cLBP), depression and PTSD symptoms, and 2) neurobiological and related neuropsychological mechanisms by which our exercise-training paradigm may foster exercise maintenance. More specifically, the investigators hypothesize relationships between exercise-training associated augmentation of neuropeptide Y (NPY) system function and improved capacities for reward and self-regulation-neuropsychological capacities posited to underlie intrinsic motivation and self-efficacy, which in turn have been shown to predict exercise maintenance. This study will focus on Veterans with cLBP/PTSD. The study design includes a baseline, acute, cardiopulmonary exercise assessment (CPX) that will inform the exercise prescription for the 12-week "progressive exercise" training program, comprised of three 30-45 minute in clinic exercise sessions per week (walking or running--depending on the ability/capacity of the participant). All exercise sessions will be supervised by an exercise physiologist in the Clinical Studies Unit (CSU) at VA Boston Healthcare System. Intermittent telephone calls by the researchers will provide additional motivational support and problem solving. Implementation of the prescribed exercise regimen will also be supported by the use of heart rate and actigraph monitors programmed for the participant to achieve their prescribed heart rate range (HRR). Also, a "midpoint" and "endpoint" CPX assessment will track changes in NPY system function and delineate their impact on pain, depression and PTSD symptoms, as well as the factors proposed to foster exercise maintenance. All three CPX tests will be performed in accordance with guidelines published by the American College of Cardiology. Among Veterans with cLBP/PTSD, the investigators hypothesize that the capacity to release NPY in response to vigorous exercise (i.e., acute CPX testing) will be associated with improvements in pain, depression and PTSD symptoms, as well as the putative factors that predict exercise maintenance. Data from this R21 will be used to demonstrate feasibility and inform the further development of individually prescribed, motivationally based exercise regimens that could be used as adjuncts to cognitive and other therapeutic PTSD, depression or chronic pain interventions to reduce cLBP, depression and PTSD, as well as the negative consequences of these disorders over the long-term.

\*Note: mandatory covid precautions due to the pandemic led to an initial suspension of all study activities in 2020 after just one of the consented enrolled participants was randomized into the 'progressive exercise' study arm. That participant completed only half of the 12 week intervention. In addition, this participant had one adverse event after a stress test which was determined to be unrelated to the study intervention. Despite intentions to resume the research, a decision was made to terminate the study in early 2022 given the recruitment and intervention challenges with the pandemic surge and the end of funding. No data wee collected related to any of the study outcome measures so no outcome measures are reported.

Eligibility criteria: Inclusion Criteria:

1. ICD-9 or ICD-10 diagnosis of chronic low back pain, as confirmed by the rehabilitation medicine doctor consulting to the study, and a confirmed comorbid psychiatric diagnosis of PTSD. More specifically, the CLBP/PTSD participant must meet for current chronic PTSD (\>3 months) as assessed by the CAPS-5, 1-Month Diagnostic Version.
2. A medical history, physical examination, vital signs, EKG, and baseline laboratory studies, including urine toxicology screens and a negative urine pregnancy test (woman only), indicate that symptom-limited cardiopulmonary exercise stress (CPX) testing will be safe.
3. Women of child bearing capacity must agree to use effective contraception while participating; a urine pregnancy test performed on the morning prior to completing CPX testing will also be done.
4. Relatively sedentary at enrollment, as defined by the American College of Sports Medicine (i.e., performing less than 30 minutes/day and less than 150 minutes per week of moderate physical activity).
5. Free of medications and other substances (e.g., illicit drugs and alcohol) with effects that could hinder data interpretation for 2-6 weeks before the cold pressor test (CPT) and CPX testing depending on the medication and frequency of use (which must be cleared by the study Co-I and study MD, Dr. Rasmusson).
6. Psychotropic medications are allowed, as long as the participant has been stable on them for two months.
7. Tobacco product use is allowed; participants will not be required to lower or stop their dosage/intake; intensity of smoking will be monitored across the study via use of urine testing for cotinine (a long-lived metabolite of nicotine) at each test session. Regular morning nicotine users will be instructed to smoke/chew to satisfaction just prior to arriving at the Clinical Studies Unit for testing, which will be approximately 2-3 hours prior to performance of the CPT and CPX.
8. Using pain medications other than opiates provided none taken for 5 half-lives before CPT/CPX testing, generally about 24 hours.
9. Other anxiety or depressive disorders are permitted
10. May be involved in supportive psychotherapies as long as their participation has been stable for 3 months prior to study entry and remains stable throughout the course of the study
11. Can have a mild to moderate TBI, as determined by the BAT-L assessment.
12. Taking medications for chronic psychiatric or medical illnesses is allowed as long as the medications and medication dosing are stable for two months prior to participation in the study and remain stable throughout the 12 week exercise training protocol and final exercise test.

Exclusion Criteria:

1. A life threatening or acute physical illness (e.g., cancer), current schizophreniform illnesses, bipolar disorder, or active suicidal or homicidal ideation requiring clinical intervention.
2. Current or past alcohol and/or substance dependence (less than three months from date of screening assessment)
3. Current opiate pain medication use
4. Women who are or are planning to become pregnant within the next six months
5. Individuals seeking pain treatment such as surgical interventions or who have a neuropathic origin to their pain
6. Cannot tolerate exercising on a treadmill or on an upright bike due to chronic pain
7. A clinical history of coronary artery disease or positive stress test, uncontrolled cardiac arrhythmia, moderate-to-severe aortic stenosis, severe arterial hypertension (systolic \>200 mmHg, diastolic\>110 mm Hg) and more than first degree atrioventricular block
8. Severe TBI, as evidenced on the VA TBI screen and the BAT-L assessment.

Primary outcomes:
measure: Transtheoretical Model of Exercise: Stages of Change (Short-form)
timeFrame: Eligibility/screening, baseline, 6 week, and 12 week
measure: ActiGraph Monitor
timeFrame: over the course of 12 weeks of exercise training
Secondary outcomes:
measure: West Haven Yale Multidimensional Pain Inventory - Pain Interference
timeFrame: Eligibility/Screening, baseline, 6 week, 12 week
measure: Clinician-Administered PTSD Scale-5
timeFrame: Eligibility/screening and 12 week
Other outcomes:
measure: Self-Efficacy for Exercise
timeFrame: Eligibility/Screening, baseline, 6 week, 12 week
measure: Generalized Self-Efficacy Scale
timeFrame: Eligibility/Screening, baseline, 6 week, 12 week
measure: Temporal Experience of Pleasure Scale
timeFrame: Eligibility/Screening, baseline, 6 week, 12 week
measure: Effort Expenditure for Rewards Task
timeFrame: Eligibility/Screening, baseline, 6 week, 12 week
measure: Neuropeptide-Y
timeFrame: Baseline, 6 week, 12 week
measure: Go/No-Go Task
timeFrame: Baseline, 6 week, 12 week
measure: Exercise Motivation Scale
timeFrame: Eligibility/Screening, baseline, 6 week, 12 week
measure: Beck Depression Inventory
timeFrame: Eligibility/Screening, baseline, 6 week, 12 week
Locations:
city: Jamaica Plain
country: United States
facility: VA Boston Healthcare System
state: Massachusetts
Study officials:
affiliation: Boston University
name: Erica R Scioli, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Scioli ER, Smith BN, Whitworth JW, Spiro A, Esterman M, Dutra S, Bogdan KM, Eld A, Rasmusson AM. Moderated mediation for exercise maintenance in pain and posttraumatic stress disorder: A randomized trial. Health Psychol. 2020 Sep;39(9):826-840. doi: 10.1037/hea0000876.