Proof of Concept Study to Treat Negative Affect in Chronic Low Back Pain
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 308
- 试验地点
- 3
- 主要终点
- "Composite Responder", Involving the Domains of Pain, Function, and Depression. See "Other Pre-Specified Outcomes" for Description of These Sub-components.
研究概览
简要总结
This study will examine how the use of antidepressant, physical therapy, and combination of both affects pain, function, and depression outcomes in chronic low back pain patients.
详细描述
Approximately 20 million Americans are affected by chronic low back pain and negative affective states such as depression and anxiety. These negative states have all been associated with higher pain intensity, lower pain tolerance, greater use of pain medication, poor pain treatment responses, and higher levels of psychiatric comorbidity among low back pain patients. To improve these outcomes for those who suffer from low back pain, it is important to implement multiple methods with a focus in treating negative affect for pain management rather than using opioids alone.
Antidepressant (AD) and fear avoidance-based physical therapy (EFAR) have individually shown to be promising methods for pain management. In this study, AD, EFAR, and the combination therapy of the two treatments will be explored and implemented to investigate their effectiveness in improving pain, function, depression, and anxiety. The key innovation is testing a new and effective multimodal treatment that can help manage pain, as well as address negative affect.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 18-75
- •Pain duration > 6 months
- •Must meet the minimum criteria for cognitive function using the PROMIS 2-item cognitive screener (>3)
- •Average pain score of > 3/10, with low back pain being the primary pain site
- •CLBP meeting Quebec Task Force Classification System categories I-III (from axial pain only to pain radiating beyond the knee without neurological signs). Constant radicular pain associated with sensory loss is highly treatment resistant without surgery
- •In the investigator's judgment, evidence of healthcare seeking for low back pain.
- •Must meet criteria for high negative affect at 1st study visit: at least 5 on the PHQ-4 (also called the PHQ-2 + GAD-2). Scores above this level are highly associated with having a co-morbid major depression or generalized anxiety disorder diagnosis PHQ-4 scores are used as a proxy for high scores on PROMIS depression and anxiety scales
- •Having accessible electronic medical records from UPMC, Brigham and Women's Hospital, or Mayo Clinic, Rochester.
- •For those taking opioids (the opioid subgroup), participants must be prescribed opioids currently for at least 3 consecutive months prior to enrollment. Patients must be on opioids for a minimum of three months, taking them on a daily basis or intermittently during the week. The investigators will include those on strong opioids, such as oxycodone and weak opioids, such as tramadol.
- •Subject must agree that opioids cannot be increased during the study
- •For those taking opioids, no active substance use disorder in the past year as determined by the PI with the use of the Tobacco, Alcohol, Prescription Medications, and Other Substance Tool (TAPS) and a urine toxicology screen. The exceptions are tobacco, medical marijuana use in Pennsylvania or Minnesota, recreational or medical marijuana in the Boston site, or mild prescription opioid use disorder such as opioid misuse
- •No acute suicidality or history of major thought disorder (such as mania or psychosis). This will be assessed at study entry which will also include a review of history in EPIC/EMR
- •Must possess a mobile device or tablet that can send and receive text messages and access the internet
排除标准
- •Back surgery within the past six months
- •Active worker's compensation or litigation claims
- •New pain and/or psychiatric treatments within 2 weeks of enrollment
- •Intent to add new or increase pain treatments during the study period, such as back surgery, nerve block procedures, or medications
- •Intent to add new psychiatric treatments during the first 4 months of the study
- •Any clinically unstable systemic illness that is judged to interfere with the trial
- •History of cardiac, nervous system, or respiratory disease that, in the investigator's judgment, precludes participation in the study because of a heightened potential for respiratory depression
- •Non-ambulatory status
- •Pregnancy or the intent to become pregnant during the study. Women of childbearing potential will all submit a urine sample pregnancy testing at enrollment.
- •Not fluent in English and/or not able to complete the questionnaires
研究组 & 干预措施
Antidepressant (AD)
Subjects will be randomly assigned to receive the antidepressant medication for 4 months prescribed by a psychiatrist or an advanced practice provider supervised by a psychiatrist. During Phase 1 phone calls every 2 weeks or in person visits will be used to evaluate the treatment and adjust the medication. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1)
Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
干预措施: Antidepressant (Drug)
Enhanced Fear Avoidance Rehabilitation (EFAR)
Subjects will be randomly assigned to receive 8, 1-hour fear avoidance rehabilitation sessions conducted by a physical or occupational therapist, consisting of therapy sessions, pain education, and motivational messaging via a pain education self-help app for 4 months. Trained physical/occupational therapists will determine the activities as part of the treatment. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1).
Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
干预措施: Enhanced Fear Avoidance Rehabilitation (Other)
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
Subjects will receive a combination of antidepressant medication and EFAR for the first 4 months (Phase 1). In the 2nd 4 months (Phase 2) the AD treatment will be continued at the same dose(s) and they will be asked to maintain a home exercise program. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1). No re-randomization will be done in this treatment group.
干预措施: Antidepressant (Drug)
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
Subjects will receive a combination of antidepressant medication and EFAR for the first 4 months (Phase 1). In the 2nd 4 months (Phase 2) the AD treatment will be continued at the same dose(s) and they will be asked to maintain a home exercise program. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1). No re-randomization will be done in this treatment group.
干预措施: Enhanced Fear Avoidance Rehabilitation (Other)
AD -> EFAR
Subjects will be randomly assigned to receive the antidepressant medication for 4 months prescribed by a psychiatrist or an advanced practice provider supervised by a psychiatrist. During Phase 1 phone calls every 2 weeks or in person visits will be used to evaluate the treatment and adjust the medication. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1)
Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months. Those re-randomized to EFAR for 4 months will receive 8 treatment visits. The same opioid weaning process will be followed as in Phase 1.
干预措施: Antidepressant (Drug)
AD -> EFAR
Subjects will be randomly assigned to receive the antidepressant medication for 4 months prescribed by a psychiatrist or an advanced practice provider supervised by a psychiatrist. During Phase 1 phone calls every 2 weeks or in person visits will be used to evaluate the treatment and adjust the medication. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1)
Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months. Those re-randomized to EFAR for 4 months will receive 8 treatment visits. The same opioid weaning process will be followed as in Phase 1.
干预措施: Enhanced Fear Avoidance Rehabilitation (Other)
EFAR -> AD
Subjects will be randomly assigned to receive 8, 1-hour fear avoidance rehabilitation sessions conducted by a physical or occupational therapist, consisting of therapy sessions, pain education, and motivational messaging via a pain education self-help app for 4 months. Therapists will determine the activities as part of the treatment. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1).
Non-responders at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months (Phase 2). Those re-randomized to receive AD will be prescribed medications by a psychiatrist or an advanced practice provider supervised by a psychiatrist. Phone calls every 2 weeks or in person visits will be used to evaluate the treatment and adjust the medication.
The same opioid weaning process will be followed as in Phase 1.
干预措施: Antidepressant (Drug)
EFAR -> AD
Subjects will be randomly assigned to receive 8, 1-hour fear avoidance rehabilitation sessions conducted by a physical or occupational therapist, consisting of therapy sessions, pain education, and motivational messaging via a pain education self-help app for 4 months. Therapists will determine the activities as part of the treatment. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1).
Non-responders at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months (Phase 2). Those re-randomized to receive AD will be prescribed medications by a psychiatrist or an advanced practice provider supervised by a psychiatrist. Phone calls every 2 weeks or in person visits will be used to evaluate the treatment and adjust the medication.
The same opioid weaning process will be followed as in Phase 1.
干预措施: Enhanced Fear Avoidance Rehabilitation (Other)
结局指标
主要结局
"Composite Responder", Involving the Domains of Pain, Function, and Depression. See "Other Pre-Specified Outcomes" for Description of These Sub-components.
时间窗: Baseline vs. 4th month of study
To create the "composite responder" measure, Pain+ function changes will be 1 meaure, and the response rate to depression will be the 2nd component, which simplifies the assessment of multi-domain responses. We will determine the "composite responder" rate of multimodal vs. single-modal treatment primarily, and then between each arm secondarily, along with the subcomponents. The "composite responder" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1. A participant could be a pain+function responder, a depression responder, both, or neither. We use standard benchmarks for determining responses in each domain. The primary outcome is the rate of response vs. non-response on the "Composite Responder" measure. It will be expressed as percentiles in each category. We will also report the rate of pain+function responders and the rate of depression responders (other pre-specified outcomes).
"Composite Responder", involving the domains of pain, function, and depression. See "Other Pre-Specified Outcomes" for description of these sub-components.
时间窗: Baseline vs. 4th month of study
To create the "composite responder" measure, Pain+ function will form a "combined responder" metric, and the response rate to depression will be measured as well. This is done to simplify the assessment of multi-domain responses. We took this "composite responder" approach since pain, function and depression are inherently related to each other in this patient group with CLBP and high negative affect. "Combined response" and "depression response" will be integrated to determine the "composite responder" rate. A participant could be a combined responder, a depression responder, both, or neither. We use standard benchmarks for determining response vs. non-response to each domain. The primary outcome is the rate of response vs. non-response on the "Composite Responder" measure. It will be expressed as percentiles in each category. We will also report the rate of combined responders (pain+function measure) and the rate of depression responders (other pre-specified outcomes).
次要结局
- Change From Baseline Pain Interference at 4 Months Using PROMIS(Baseline vs. 4 months)
- Change From Baseline Anxiety at 4 Months Using PROMIS(Baseline vs. 4 months)
- Change From Baseline Sleep Disturbance at 4 Months Using PROMIS(Baseline vs. 4 months)
- Change From Baseline Subject's Perception of Change From Treatment at 4 Months Using Patient Global Impression of Change (PGIC)(Baseline vs. 4 months)
- Neuropathic Pain Symptoms Change, Baseline vs. 4 Months(Baseline vs. 4 months)
- Fear Avoidance Beliefs, Baseline vs. 4 Months(Baseline vs. 4 months)
- Change in PROMIS Fatigue Score From Baseline vs. 4 Months(Baseline vs. 4 months)
- WPI Symptom Severity Score(Baseline to 4 months)
- Widespread Pain Index(Baseline vs. 4 months)
- Change from Baseline Anxiety at 4 months using PROMIS(Baseline vs. 4 months)
- Change from Baseline Pain Interference at 4 months using PROMIS(Baseline vs. 4 months)
- Neuropathic pain symptoms change, baseline vs. 4 months(Baseline vs. 4 months)
- Change from Baseline Sleep Disturbance at 4 months using PROMIS(Baseline vs. 4 months)
- Change from Baseline Subject's Perception of Change from Treatment at 4 months using Patient Global Impression of Change (PGIC)(Baseline vs. 4 months)
- Change in PROMIS Fatigue score from baseline vs. 4 months(Baseline vs. 4 months)
- Fear avoidance beliefs, baseline vs. 4 months(Baseline vs. 4 months)
研究者
Ajay Wasan, MD, Msc
Professor
University of Pittsburgh