Back Pain, Low, Back Pain Lower Back Chronic, Chronic Pain
Conditions
Keywords
Placebo, Back, Pain, Chronic, Mind-Body
Brief summary
Participants with chronic back pain will complete an online prescreen. They will then be randomized to one of two different studies: a placebo vs. waitlist study or a psychotherapy vs. waitlist study, with randomization stratified on pain intensity, age, gender, and opioid use. Participants will then complete an in-person eligibility session, and eligible participants will be scheduled for the baseline assessment session. Following the baseline assessment session, participants will then be randomized to the treatment group or the waitlist group (with a ratio of 2:1 treatment:waitlist), using a computer-generated random sequence. This scheme will result in three equally sized groups-placebo, psychotherapy, and waitlist-as the investigators will collapse data from the waitlist arms in the two studies for analyses. The investigators do not use a standard three-way randomization because the investigators do not want placebo participants to think they are in a control condition. Thus, the investigators constrain participant's expectations to either injection vs. waitlist or to psychotherapy vs. waitlist. The placebo treatment is a subcutaneous injection of saline into the back. Participants will know that the treatment is a placebo, i.e., it is an open label placebo. Psychotherapy (8 sessions) will be supervised by Alan Gordon and Howard Schubiner. Functional MRI brain imaging, self-reported clinical outcomes, and behavioral measures will be collected pre- and post-treatment. A brief follow-up survey will be sent at months 1, 2, 3, 6, and 12 after the final assessment session. These will provide longer term data about the trajectory and durability of patient improvement. Additionally, a group of healthy controls, with no history of back pain, will complete the baseline assessment. They will serve as a comparison group to probe whether the patterns of observed brain activity is specific to CBP patients.
Interventions
OTHEROpen-Label Placebo Treatment for Chronic Back Pain
Subcutaneous injection of 1ml medical grade saline into the lower back.
BEHAVIORALPsychotherapy Treatment for Chronic Back Pain
Twice weekly 50 minute psychotherapy sessions for 4 weeks, plus an initial medical history session
Sponsors
Radiological Society of North America
National Institutes of Health (NIH)
Psychophysiologic Disorders Society
Foundation for the Science of Therapeutic Encounter
University of Colorado, Boulder
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Researchers will not know which treatment the participants will be receiving (placebo or psychotherapy).
Intervention model description
Participants will be randomized to one of two different studies: a placebo vs. waitlist study or a psychotherapy vs. waitlist study, with randomization stratified on pain intensity, age, gender, and opioid use. After an eligibility session, eligible participants will be randomized to the treatment group or the waitlist group (with a ratio of 2:1 treatment:waitlist), using a computer-generated random sequence. This scheme will result in three equally sized groups-placebo, psychotherapy, and waitlist-as the investigators will collapse data from the waitlist arms in the two studies for analyses. The investigators do not use a standard three-way randomization because the investigators do not want placebo participants to think they are in a control condition. Thus, the investigators constrain participant's expectations to either injection vs. waitlist or to psychotherapy vs. waitlist.
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants aged 21 to 70 with CBP will be enrolled. * CBP will be defined according to the criteria established by a recent NIH task force (Deyo et al., 2014). Pain duration must be at least 3 months, with back pain being an ongoing problem for at least half the days of the last 6 months. That is, patients can meet criteria by either reporting pain every day for the past 3 months, or by reporting pain on half or more of the days for the past 6+ months. This will be determined by asking patients: (1) How long has back pain has been an ongoing problem for you? (2) How often has low back pain been an ongoing problem for you over the past 6 months? A response of greater than 3 months to question 1 and a response of ''at least half the days in the past 6 months'' to question 2 would define CBP. * Patients must rate pain intensity at 40/100 or greater on the Brief Pain Inventory-Short Form (BPI-SF), in keeping with inclusion criteria from previous CBP trials (Baliki et al., 2012; Cherkin et al., 2016; Hashmi et al., 2013; Seminowicz et al., 2011). * Back pain must be elicited by our back pain device (see below). * Participants must also be comfortable and able to communicate via email or text message, as several study measures are collected in this manner (see below).
Exclusion criteria
* Back pain associated with compensation or litigation issues as determined by self-report within the past year. * Leg pain is greater than back pain. This suggests neuropathic pain, which may be less responsive to placebo or psychotherapy. * Difficulty participating for technical/logistical issues (e.g., unable to get to assessment sessions). * Self-reported diagnoses of schizophrenia, multiple personality disorder, or dissociative identity disorder. * Self-reported use of intravenous drugs, due to concerns about infections and subject compliance with experimental protocols. * Inability to undergo MRI as determined by MRI safety screen (e.g., pregnancy, metal in body, claustrophobia, using the standard screen conducted by the MRI imaging facility). * Hypersensitive or hyposensitive to pressure pain: unable to tolerate 7kg/cm2 stimulation or reporting no pain for 4kg/cm2 stimulation; see further details below. * Current regular use of an immunosuppressant drug, such as steroids. Such drugs interfere with immunoassay results. * Self-reported history of metastasizing cancers-cancer of the breast, thyroid, lung, kidney, prostate or blood cancers. * Self-reported history of stroke, brain surgery, or brain tumor. * Self-reported diagnosis of a specific inflammatory disorder: rheumatoid arthritis, polymyalgia rheumatica, scleroderma, Lupus, or polymyositis. * Unexplained, unintended weight loss of 20 lbs. or more in the past year. * Cauda Equina syndrome, as screened for by self-reported inability to control bowel or bladder function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brief Pain Inventory-Short Form (BPI-SF) | At post-treatment fMRI session, approximately 1 month after randomization | 1-week average pain intensity, 0 - 10 numerical rating scale, where a higher score indicates more pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PROMIS- Depression | At post-treatment fMRI session, approximately 1 month after randomization | Questionnaire measuring depression (8 items). Scores range from 8-32. A higher score indicates higher levels of depressive symptoms |
| Tampa Scale of Kinesiophobia (TSK) | At post-treatment fMRI session, approximately 1 month after randomization | Questionnaire used to assess the subjective rating of kinesiophobia or fear of movement. Scores range from 11-44 with higher scores indicating greater fear of pain, movement, and injury. |
| Pain Catastrophizing Questionnaire (PCS) | At post-treatment fMRI session, approximately 1 month after randomization | Questionnaire used to help quantify an individual's pain experience. Measured 0-52. A higher score means a higher level of catastrophizing. |
| Timeline Follow-Back Measure for Alcohol (TLFB) | At post-treatment fMRI session, approximately 1 month after randomization | Questionnaire used to assess daily drinking (number of drinks consumed over past two weeks) |
| Patient Global Impression of Change (PGIC) | At post-treatment fMRI session, approximately 1 month after randomization | Post-treatment-only outcome measure depicting a patient's subjective rating of overall improvement. Score ranges from 1-7 with a higher score indicating a higher level of change and improvement |
| Treatment Satisfaction Questionnaire | At post-treatment fMRI session, approximately 1 month after randomization | Post-treatment-only outcome measure depicting the patient's satisfaction with the treatment. Measured 0 - 100. A higher score means higher satisfaction with treatment/ |
| Positive Affect Scale Short Form (PANAS-SF) | At post-treatment fMRI session, approximately 1 month after randomization | Questionnaire to rate positive affect, scores range from 5 - 25, a higher score means stronger affect |
| Negative Affect Scale Short Form (PANAS-SF) | At post-treatment fMRI session, approximately 1 month after randomization | Questionnaire to rate negative affect, scores range from 5 - 25, with a higher score meaning a stronger negative affect |
| PROMIS Anger | At post-treatment fMRI session, approximately 1 month after randomization | Questionnaire measuring anger (5 items) with a score range of 5-25. Higher scores indicate a higher severity of anger. |
| PROMIS Sleep | At post-treatment fMRI session, approximately 1 month after randomization | Questionnaire measuring sleep disturbance (8 items). Scores range from 8-40. Higher scores indicate higher levels of sleep disturbance |
| PROMIS Anxiety | At post-treatment fMRI session, approximately 1 month after randomization | Questionnaire measuring anxiety (8 items). Scores range from 8-40 with a higher score meaning more severe levels of fear, anxious misery, hyperarousal, and somatic symptoms related to arousal. |
| Timeline Follow-Back Measure for Opioid Use (TLFB) | At post-treatment fMRI session, approximately 1 month after randomization | Questionnaire used to assess daily opioid use (number of pills consumed over past two weeks) |
| Timeline Follow-Back Measure for Cannabis (TLFB) | At post-treatment fMRI session, approximately 1 month after randomization | Questionnaire used to assess daily cannabis use (number of grams consumed over past two weeks) |
| Oswestry Disability Index | At post-treatment fMRI session, approximately 1 month after randomization | Back pain disability questionnaire measured on a scale of 0-100. A higher score indicates a higher severity of disability. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pain Reprocessing Therapy (PRT) Received psychological treatment | 50 |
| Placebo Open-label placebo | 51 |
| Usual Care Continue usual care | 50 |
| Total | 151 |
Baseline characteristics
| Characteristic | Pain Reprocessing Therapy (PRT) | Placebo | Usual Care | Total |
|---|---|---|---|---|
| Age, Continuous | 42.6 years STANDARD_DEVIATION 16.2 | 39.4 years STANDARD_DEVIATION 14.9 | 41.3 years STANDARD_DEVIATION 15.9 | 41.1 years STANDARD_DEVIATION 15.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 49 Participants | 48 Participants | 147 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 46 Participants | 45 Participants | 43 Participants | 134 Participants |
| Sex: Female, Male Female | 29 Participants | 25 Participants | 27 Participants | 81 Participants |
| Sex: Female, Male Male | 21 Participants | 26 Participants | 23 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 51 | 0 / 50 |
| other Total, other adverse events | 0 / 50 | 0 / 51 | 0 / 50 |
| serious Total, serious adverse events | 0 / 50 | 0 / 51 | 0 / 50 |
Outcome results
Primary
Brief Pain Inventory-Short Form (BPI-SF)
1-week average pain intensity, 0 - 10 numerical rating scale, where a higher score indicates more pain.
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | Brief Pain Inventory-Short Form (BPI-SF) | 1.18 units on a scale | Standard Deviation 1.24 |
| Placebo | Brief Pain Inventory-Short Form (BPI-SF) | 2.84 units on a scale | Standard Deviation 1.64 |
| Usual Care | Brief Pain Inventory-Short Form (BPI-SF) | 3.13 units on a scale | Standard Deviation 1.45 |
Secondary
Negative Affect Scale Short Form (PANAS-SF)
Questionnaire to rate negative affect, scores range from 5 - 25, with a higher score meaning a stronger negative affect
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | Negative Affect Scale Short Form (PANAS-SF) | 8.30 score on a scale | Standard Deviation 3.04 |
| Placebo | Negative Affect Scale Short Form (PANAS-SF) | 7.70 score on a scale | Standard Deviation 2.44 |
| Usual Care | Negative Affect Scale Short Form (PANAS-SF) | 8.19 score on a scale | Standard Deviation 2.75 |
Secondary
Oswestry Disability Index
Back pain disability questionnaire measured on a scale of 0-100. A higher score indicates a higher severity of disability.
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | Oswestry Disability Index | 10.14 score on a scale | Standard Deviation 10.63 |
| Placebo | Oswestry Disability Index | 19.00 score on a scale | Standard Deviation 11.07 |
| Usual Care | Oswestry Disability Index | 20.68 score on a scale | Standard Deviation 10.68 |
Secondary
Pain Catastrophizing Questionnaire (PCS)
Questionnaire used to help quantify an individual's pain experience. Measured 0-52. A higher score means a higher level of catastrophizing.
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | Pain Catastrophizing Questionnaire (PCS) | 8.30 score on a scale | Standard Deviation 3.04 |
| Placebo | Pain Catastrophizing Questionnaire (PCS) | 7.70 score on a scale | Standard Deviation 2.44 |
| Usual Care | Pain Catastrophizing Questionnaire (PCS) | 8.19 score on a scale | Standard Deviation 2.75 |
Secondary
Patient Global Impression of Change (PGIC)
Post-treatment-only outcome measure depicting a patient's subjective rating of overall improvement. Score ranges from 1-7 with a higher score indicating a higher level of change and improvement
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | Patient Global Impression of Change (PGIC) | 6.14 score on a scale | Standard Deviation 0.88 |
| Placebo | Patient Global Impression of Change (PGIC) | 3.61 score on a scale | Standard Deviation 1.62 |
| Usual Care | Patient Global Impression of Change (PGIC) | 2.06 score on a scale | Standard Deviation 1.45 |
Secondary
Positive Affect Scale Short Form (PANAS-SF)
Questionnaire to rate positive affect, scores range from 5 - 25, a higher score means stronger affect
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | Positive Affect Scale Short Form (PANAS-SF) | 17.89 score on a scale | Standard Deviation 3.38 |
| Placebo | Positive Affect Scale Short Form (PANAS-SF) | 15.20 score on a scale | Standard Deviation 5.6 |
| Usual Care | Positive Affect Scale Short Form (PANAS-SF) | 14.98 score on a scale | Standard Deviation 3.5 |
Secondary
PROMIS Anger
Questionnaire measuring anger (5 items) with a score range of 5-25. Higher scores indicate a higher severity of anger.
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | PROMIS Anger | 9.52 score on a scale | Standard Deviation 3.91 |
| Placebo | PROMIS Anger | 9.89 score on a scale | Standard Deviation 3.81 |
| Usual Care | PROMIS Anger | 10.45 score on a scale | Standard Deviation 3.86 |
Secondary
PROMIS Anxiety
Questionnaire measuring anxiety (8 items). Scores range from 8-40 with a higher score meaning more severe levels of fear, anxious misery, hyperarousal, and somatic symptoms related to arousal.
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | PROMIS Anxiety | 15.02 score on a scale | Standard Deviation 6.16 |
| Placebo | PROMIS Anxiety | 13.89 score on a scale | Standard Deviation 5.78 |
| Usual Care | PROMIS Anxiety | 14.11 score on a scale | Standard Deviation 6.99 |
Secondary
PROMIS- Depression
Questionnaire measuring depression (8 items). Scores range from 8-32. A higher score indicates higher levels of depressive symptoms
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | PROMIS- Depression | 12.23 score on a scale | Standard Deviation 4.94 |
| Placebo | PROMIS- Depression | 11.75 score on a scale | Standard Deviation 4.05 |
| Usual Care | PROMIS- Depression | 11.81 score on a scale | Standard Deviation 4.45 |
Secondary
PROMIS Sleep
Questionnaire measuring sleep disturbance (8 items). Scores range from 8-40. Higher scores indicate higher levels of sleep disturbance
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | PROMIS Sleep | 17.73 score on a scale | Standard Deviation 6.75 |
| Placebo | PROMIS Sleep | 20.50 score on a scale | Standard Deviation 6.17 |
| Usual Care | PROMIS Sleep | 20.89 score on a scale | Standard Deviation 6.02 |
Secondary
Tampa Scale of Kinesiophobia (TSK)
Questionnaire used to assess the subjective rating of kinesiophobia or fear of movement. Scores range from 11-44 with higher scores indicating greater fear of pain, movement, and injury.
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | Tampa Scale of Kinesiophobia (TSK) | 16.41 score on a scale | Standard Deviation 5.37 |
| Placebo | Tampa Scale of Kinesiophobia (TSK) | 22.16 score on a scale | Standard Deviation 4.94 |
| Usual Care | Tampa Scale of Kinesiophobia (TSK) | 22.51 score on a scale | Standard Deviation 6.3 |
Secondary
Timeline Follow-Back Measure for Alcohol (TLFB)
Questionnaire used to assess daily drinking (number of drinks consumed over past two weeks)
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | Timeline Follow-Back Measure for Alcohol (TLFB) | 11.63 Drinks | Standard Deviation 10.83 |
| Placebo | Timeline Follow-Back Measure for Alcohol (TLFB) | 12.88 Drinks | Standard Deviation 14.3 |
| Usual Care | Timeline Follow-Back Measure for Alcohol (TLFB) | 8.02 Drinks | Standard Deviation 10.63 |
Secondary
Timeline Follow-Back Measure for Cannabis (TLFB)
Questionnaire used to assess daily cannabis use (number of grams consumed over past two weeks)
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | Timeline Follow-Back Measure for Cannabis (TLFB) | 6.76 Grams of cannabis | Standard Deviation 25.32 |
| Placebo | Timeline Follow-Back Measure for Cannabis (TLFB) | 3.31 Grams of cannabis | Standard Deviation 6.72 |
| Usual Care | Timeline Follow-Back Measure for Cannabis (TLFB) | 1.49 Grams of cannabis | Standard Deviation 3.2 |
Secondary
Timeline Follow-Back Measure for Opioid Use (TLFB)
Questionnaire used to assess daily opioid use (number of pills consumed over past two weeks)
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | Timeline Follow-Back Measure for Opioid Use (TLFB) | 1.29 Opioid pills | Standard Deviation 4.5 |
| Placebo | Timeline Follow-Back Measure for Opioid Use (TLFB) | 0.36 Opioid pills | Standard Deviation 2.11 |
| Usual Care | Timeline Follow-Back Measure for Opioid Use (TLFB) | 1.77 Opioid pills | Standard Deviation 8.99 |
Secondary
Treatment Satisfaction Questionnaire
Post-treatment-only outcome measure depicting the patient's satisfaction with the treatment. Measured 0 - 100. A higher score means higher satisfaction with treatment/
Time frame: At post-treatment fMRI session, approximately 1 month after randomization
Population: all available participants analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Reprocessing Therapy (PRT) | Treatment Satisfaction Questionnaire | 92.40 score on a scale | Standard Deviation 8.01 |
| Placebo | Treatment Satisfaction Questionnaire | 57.61 score on a scale | Standard Deviation 23.05 |
| Usual Care | Treatment Satisfaction Questionnaire | 36.86 score on a scale | Standard Deviation 23.01 |