Clinical trial NCT04142177: Sequential and Comparative Evaluation of Pain Treatment Effectiveness Response
Official title: CSP #2009 - Sequential and Comparative Evaluation of Pain Treatment Effectiveness Response: The SCEPTER Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Low Back Pain
Keywords: chronic low back pain
severe low back pain
pain
non-pharmacological treatment
self-management
physical therapy
exercise
yoga
cognitive behavioral therapy
spinal manipulation therapy
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2019-10-29
Enrollment: 2529
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: sequential randomized, pragmatic, 2-step comparative effectiveness study design
Primary purpose: TREATMENT

Brief summary: VETERANS ONLY. Chronic low back pain (cLBP) is common. Most Americans will have at least one episode of low back pain in their lifetimes. Approximately 50% of all US Veterans have chronic pain, and CLBP is the most common type of pain in this population. This study will use a sequential randomized, pragmatic, 2-step comparative effectiveness study design. The main goal is to identify the best approach for treating cLBP using commonly recommended non-surgical and non-pharmacological options. The first step compares continued care and active monitoring (CCAM) to internet-based pain self-management (Pain EASE) and an enhanced physical therapy intervention that combines Pain EASE with tailored exercise and physical activity. Patients who do not have a significant decrease in pain interference (a functional outcome) in Step 1 and those desiring additional treatment will be randomized in Step 2 to yoga, spinal manipulation therapy (SMT), or therapist-delivered cognitive behavioral therapy (CBT). Participants proceeding to randomization in Step 2 will be allowed to exclude up to one of the three Step 2 treatments based on their preferences. The investigators' primary hypothesis for the first treatment step is that an enhanced physical therapy intervention that combines pain self-management education with a tailored exercise program will reduce pain interference greater than internet-based pain self-management alone or CCAM in Veterans with cLBP. The primary outcome is change in pain interference at 3 months, measured using the Brief Pain Inventory (BPI) pain interference subscale. Study participants will be followed for one year after initiation of their final study treatments to assess the durability of treatment effects. The study plans to randomize 2529 patients across 20 centers.

Detailed description: Chronic low back pain (cLBP) is common. The point prevalence of low back pain in the US is about 25%, and the majority of Americans will have at least one episode of low back pain in their lifetimes. Approximately 50% of all US Veterans have chronic pain, and cLBP is the most common type of pain in this population. Low back pain is the second most common condition leading patients to seek a physician's care. In addition, cLBP is costly. Healthcare expenditure for low back pain in the US is greater than $30 billion per year, and total expenditures including the cost of disability approach $100 billion per year. In fact, low back pain is the most common cause of work-related disability and is a major cause of service- connected disability amongst US Veterans. Making matters worse, the US is in the midst of a growing opioid abuse epidemic having its roots in the lack of understanding of how to effectively treat cLBP and other common forms of acute and chronic pain.

Using a sequential randomized, pragmatic, 2-step comparative effectiveness study design, the main goal is to identify the optimal approach to cLBP treatment employing commonly recommended non-surgical, non-pharmacological options. Options for treatment in this trial were selected based on the VA's stepped-care model for the treatment of chronic pain, availability of treatments, controversies in current clinical practice, and the surveyed preferences of both Veterans with cLBP and VA healthcare providers. The implementation of study results has been kept closely in mind, and stakeholder input has been incorporated.

The first step compares continued care and active monitoring arm (CCAM) to internet-based pain self-management (Pain EASE) and an enhanced physical therapy intervention that combines Pain EASE with tailored exercise and physical activity. The utility of tailored exercise requiring physical therapist guidance added to internet-based self-management has not been examined. A CCAM arm is included in this step to definitively assess the effectiveness of these initial treatment options. Patients failing to achieve clinically significant reductions in pain interference (a functional outcome) in Step 1 and those desiring additional treatment will be randomized in Step 2 to yoga, spinal manipulation therapy (SMT), or therapist-delivered cognitive behavioral therapy (CBT). These options appear in consensus guidelines although little information is available to help patients and providers select the most effective option. Each option has a distinct theoretical basis for effectiveness with yoga described as a mind-body therapy, SMT as a technique to adjust the structural relationships of the spine, and CBT as a psychological or behavioral approach. While the literature suggests approximate clinical equipoise between these treatments, costs, side effects, access to specific options and patient/provider acceptance may differ significantly. Participants proceeding to randomization in Step 2 will be allowed to exclude up to one of the three Step 2 treatments based on their preferences.

The investigators' primary hypothesis corresponding to the first treatment step is that an enhanced physical therapy intervention that combines pain self-management education with a tailored exercise program will reduce pain interference greater than internet-based pain self-management alone or CCAM in Veterans with cLBP. For the second step, the study has been powered to detect clinically meaningful pairwise differences among the three treatments. The primary outcome is change in pain interference at 3 months, measured using the Brief Pain Inventory (BPI) pain interference subscale. This is a widely accepted functional outcome in musculoskeletal pain trials and emphasizes an endpoint important to patients, providers and healthcare management systems. Study participants will be followed for one year after initiation of their final study treatments to assess the durability of treatment effects.

The investigators will leverage the power of this large study and maximize its impact by incorporating additional outcome measures as recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consortium and other pain trials consensus groups. These secondary outcomes include pain severity, physical functioning, depression, anxiety, fatigue, sleep, global impression of change, and quality of life. The investigators will evaluate the impact of patient characteristics, treatment preferences and expectations on study outcomes as these variables have been identified in smaller studies to modify treatment response. To derive information rapidly translatable to changes in VA care, the investigators will collect information critical for implementation of the treatment strategies under study. Key implementation factors will include treatment fidelity, treatment adherence, patient acceptance, provider acceptance, logistical feasibility, and resource requirements. Finally, a carefully designed costs and downstream budget impact aim will provide additional practical information for clinical managers and policy makers related to non-pharmacological treatments for cLBP.

The study will involve diverse VA centers with respect to geographical region, racial characteristics of the population served and facility size. The study plans to randomize 2529 patients across 20 centers. Preliminary site surveys indicate a high level of enthusiasm for the project. In addition, a query of the VA's Corporate Data Warehouse (CDW) identified more than 850,000 potential cLBP study subjects receiving regular care through VA. Twenty-five VA medical centers have more than 10,000 potentially eligible patients underscoring the high prevalence of cLBP. The investigators' pragmatic trial design will incorporate broad eligibility criteria.

Chronic low back pain is an enormous problem for the VA, the United States and many other countries. This study will provide definitive information concerning the effectiveness, costs, acceptability, and implementation of several commonly used, patient-preferred, non-pharmacological treatment options. All the selected treatment options carry relatively low levels of risk, are guideline congruent, and are consistent with stepped-care models of healthcare delivery used by the VA and other healthcare organizations. The impact on VA healthcare is expected to be large and immediate.

Eligibility criteria: Inclusion Criteria:

To be eligible to participate in this study, an individual must meet all the following criteria:

1. Low back pain

   1. present for at least 6 months,
   2. present most days or everyday,
   3. interferes the most with activities considering all of the places where the patient experiences pain;
2. Pain, Enjoyment, General Activity (PEG) score of 4 or greater;
3. Veteran age 18 years or older, either sex, any racial or ethnic background;
4. Able to comprehend and willing to sign the study informed consent form;
5. Able to attend in-person treatment sessions;
6. Anticipate continuing care at the enrolling VA for the period of the study;
7. Stable access to the internet at home, work, or other location (e.g. mobile phone), and an email address.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Currently enrolled in any other interventional study unless exempted by CSP;
2. Acute or chronic illness that would prevent the Veteran from receiving study treatments offered (e.g., uncontrolled hypertension, recent myocardial infarction within the last 6 months, unstable angina, acute congestive heart failure);
3. Neurological impairment related to disease of the spine or other causes preventing participation in any of the treatment modalities under study;
4. Current or recent (last 3 months) treatment involving Cognitive Behavioral Therapy, Spinal manipulation therapy, or Yoga;
5. Current severe alcohol or substance abuse use disorder;
6. Severe psychiatric illness (e.g. current psychosis, current suicidal ideation, or psychiatric illness requiring hospitalization within the last 6 months);
7. Undergoing evaluation for back surgery or planned back surgery;
8. Cognitive or severe hearing or visual impairment preventing participation in treatment options or outcome measure assessments;
9. Pregnancy;
10. Refusal to provide written consent.

Primary outcomes:
measure: Brief Pain Inventory (BPI) Interference scale
timeFrame: 3 months post-treatment
Secondary outcomes:
measure: Serious Adverse Events
timeFrame: 3, 6, 9, and 12 months post-treatment
measure: Brief Pain Inventory (BPI) Interference scale
timeFrame: 6, 9, and 12 months post-treatment
measure: Patient Health Questionnaire-9 (PHQ-9)
timeFrame: 3, 6, 9, and 12 months post-treatment
measure: Numeric Rating Scale (NRS)
timeFrame: 3, 6, 9, and 12 months post-treatment
measure: Roland-Morris Disability Questionnaire (RMDQ)
timeFrame: 3, 6, 9, and 12 months post-treatment
measure: Generalized Anxiety Disorder-7 Scale (GAD-7)
timeFrame: 3,6, 9, and 12 months post-treatment
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) - Sleep
timeFrame: 3, 6, 9, and 12 months post-treatment
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue
timeFrame: 3, 6, 9, and 12 months post-treatment
measure: Global Mental Health (GMH-2)
timeFrame: 3, 6, 9, and 12 months post-treatment
measure: Global Physical Health (GPH-2)
timeFrame: 3, 6, 9, and 12 months post-treatment
measure: Patient Global Impression of Change (PGIC)
timeFrame: 3,6, 9, and 12 months post-treatment
measure: EuroQol Quality of Life Scale (EQ-5D-5L)
timeFrame: 3, 6, 9, and 12 months post-treatment
measure: Non-VA Healthcare Utilization
timeFrame: 3, 6, 9, and 12 months post-treatment
measure: Societal Cost
timeFrame: 3, 6, 9, and 12 months post-treatment
measure: Follow-up Treatments and Medications
timeFrame: 3, 6, 9, and 12 months post-treatment
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix VA Health Care System, Phoenix, AZ
state: Arizona
city: Loma Linda
country: United States
facility: VA Loma Linda Healthcare System, Loma Linda, CA
state: California
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System, Long Beach, CA
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System, Palo Alto, CA
state: California
city: Aurora
country: United States
facility: Rocky Mountain Regional VA Medical Center, Aurora, CO
state: Colorado
city: Bay Pines
country: United States
facility: Bay Pines VA Healthcare System, Pay Pines, FL
state: Florida
city: Orlando
country: United States
facility: Orlando VA Medical Center, Orlando, FL
state: Florida
city: Decatur
country: United States
facility: Atlanta VA Medical and Rehab Center, Decatur, GA
state: Georgia
city: Indianapolis
country: United States
facility: Richard L. Roudebush VA Medical Center, Indianapolis, IN
state: Indiana
city: Baltimore
country: United States
facility: Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD
state: Maryland
city: Boston
country: United States
facility: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
state: Massachusetts
city: Saint Louis
country: United States
facility: St. Louis VA Medical Center John Cochran Division, St. Louis, MO
state: Missouri
city: North Las Vegas
country: United States
facility: VA Southern Nevada Healthcare System, North Las Vegas, NV
state: Nevada
city: Asheville
country: United States
facility: Asheville VA Medical Center, Asheville, NC
state: North Carolina
city: Portland
country: United States
facility: VA Portland Health Care System, Portland, OR
state: Oregon
city: San Antonio
country: United States
facility: South Texas Health Care System, San Antonio, TX
state: Texas
city: Salt Lake City
country: United States
facility: VA Salt Lake City Health Care System, Salt Lake City, UT
state: Utah
city: Hampton
country: United States
facility: Hampton VA Medical Center, Hampton, VA
state: Virginia
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center, Richmond, VA
state: Virginia
Study officials:
affiliation: VA Palo Alto Health Care System, Palo Alto, CA
name: David J Clark, PhD MD
role: STUDY_CHAIR
affiliation: Richard L. Roudebush VA Medical Center, Indianapolis, IN
name: Matthew J. Bair, MD MS
role: STUDY_CHAIR
References: