Reconsolidation Therapy With Propranolol as a Treatment for Chronic Pain

Study Overview
=================
Brief Summary
-----------------
The primary aim of this study is to document the feasibility and acceptability of an intervention consisting of pain neuroscience education and reconsolidation therapy with propranolol in adults suffering from chronic pain (chronic low back pain or fibromyalgia). The secondary aim of the study is to estimate the effect size of the intervention on pain and function one month post-intervention, and to obtain data for sample-size calculation for a subsequent randomized controlled trial.

Detailed Description
-----------------
Background: Many patients with chronic pain exhibit abnormal synaptic changes in the central nervous system - including hyperactivity in the amygdala - reminiscent of those seen in post-traumatic stress disorder (PTSD). A recently developed psychiatric treatment for PTSD involves reactivating the synapses to make them temporarily malleable and then blocking their reconsolidation with propranolol, thereby reducing the hyperactivity in the amygdala and decreasing the intensity of the symptoms in a lasting way. Considering the similarities between PTSD and chronic pain, this treatment could also be beneficial for patients with chronic pain. Objectives: The primary objective of this study will be to document the feasibility and acceptability of a combined pain neuroscience education and reconsolidation blockade intervention with oral propranolol (or placebo) in adult patients with chronic pain (specifically, low back pain or fibromyalgia). The secondary objective will be to estimate the effect size of the intervention on function and pain one month post-intervention, and to obtain the data necessary for a sample size calculation of a subsequent larger scale study. Description: The research design is a quantitative, placebo-controlled clinical trial (Phase II) feasibility study. The sample will consist of French-speaking adults with chronic low back pain or fibromyalgia (n=24 per population; 12 control and 12 experimental participants for each population; allocation by minimization); participants with a contraindication to propranolol or a neurological diagnosis will be excluded. All participants will receive education on the neuroscience of pain (video vignettes) and will participate in 6 weekly intervention sessions. During these sessions, they will receive propranolol or placebo capsules (double-blind; dosing based on size) and participate in a reactivation procedure (description and/or visualization of painful movements). Feasibility measures will be collected throughout the study; acceptability and efficacy measures will be assessed 4 weeks post-intervention, with the exception of physical function (primary efficacy measure), which will also be measured at each intervention session. Relevance: This study will be the first to use reconsolidation blockade for the treatment of chronic pain. The postulated mechanism of action is plausible and supported by scientific evidence, but to date has never been tested in humans with persistent pain. If our results demonstrate that the intervention is feasible, acceptable, and has the potential to be effective, randomized clinical trials may follow our study to robustly evaluate the effect of our intervention in the short and long term. The intervention could also be evaluated in other chronic pain populations with central sensitization, such as pelvic pain, chronic neck pain (whiplash), etc.

Official Title
-----------------
Reconsolidation Therapy With Propranolol as a Novel Treatment for Chronic Pain : a Placebo-controlled Feasibility Study

Conditions
-----------------
Chronic Low-back Pain, Fibromyalgia

Intervention / Treatment
-----------------
* Drug: Propranolol Hydrochloride
* Drug: Placebo
* Behavioral: Reactivation procedure
* Behavioral: Pain neuroscience education


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: French speaking Suffering from [chronic low back pain OR fibromyalgia] for >6 months Average pain at least 4/10 Central sensitization (assessed via a standardized physiotherapy evaluation and the Central Sensitization Inventory) Exclusion Criteria: Health condition for which propranolol is contra-indicated Medication with which co-administration of propranolol is contra-indicated Severe or uncontrolled neurological/psychiatric condition (including post-traumatic stress disorder, substance abuse, suicidal ideation, etc.) Surgery of the lower-back in the last 3 years Litigation surrounding the painful condition

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propranolol<br>Pain neuroscience education (10 short videos - 2 to 4 mins each) 6 weekly sessions of Reconsolidation therapy with propranolol. At the beginning of each session, participants will take 2 to 4 capsules of 20 mg propranolol (dose calculated based on sex and height). One hour after ingestion of the propranolol, participants will undergo a reactivation procedure, wherein they will be asked to describe/visualize painful movements/activities. | Drug: Propranolol Hydrochloride<br>* 6 weekly doses (40 to 80 mg) 1h before the reactivation procedure<br>* Other names: Experimental group;Behavioral: Reactivation procedure<br>* Description/visualization of painful movements/activities<br>Behavioral: Pain neuroscience education<br>* In the form of 10 videos that participants will watch on their own time<br>|
| Placebo Comparator: Placebo<br>Pain neuroscience education (10 short videos - 2 to 4 mins each) 6 weekly sessions of Reconsolidation therapy with a placebo. At the beginning of each session, participants will take 2 to 4 capsules of 20 mg placebo (dose calculated based on sex and height). One hour after ingestion of the placebo, participants will undergo a reactivation procedure, wherein they will be asked to describe/visualize painful movements/activities. | Drug: Placebo<br>* 6 weekly doses (40 to 80 mg) 1h before the reactivation procedure<br>* Other names: Control group;Behavioral: Reactivation procedure<br>* Description/visualization of painful movements/activities<br>Behavioral: Pain neuroscience education<br>* In the form of 10 videos that participants will watch on their own time<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility outcome 1 : Weekly recruitment rate | Number of prospective participants successfully recruited every week, vs number of participants excluded and number of refusals | Through recruitment phase (estimated 3 months per population) | 
| Feasibility outcome 2 : Rate of study completion | Percentage of sample with perfect attendance vs partial attendance vs withdrawal vs exclusion vs loss to follow-up. | Through data collection phase (estimated 6 months per population) | 
| Feasibility outcome 3 : Number of participants with adverse events (observed and self-reported) | For all adverse even, the following will be reported : Type & severity (according to the CTCAE), attribution, expected vs unexpected | Through data collection phase (estimated 6 months per population) | 
| Feasibility outcome 4 : % participants in each group who believe they received the experimental treatment (propranolol) | This percentage will be compared between the two groups to assess blinding | At follow-up (on average,12 weeks after recruitment) | 
| Acceptability outcome 1 : perceived burden of the intervention (prospective and retrospective) | Rated on an 11-point numerical rating scale (0-10; 10 = worse outcome) | Prospective rating : at baseline ; Retrospective rating : at follow-up (on average,12 weeks after recruitment) | 
| Acceptability outcome 2 : perceived ethicality of the intervention (prospective and retrospective) | Rated on an 11-point numerical rating scale (0-10; 10 = better outcome) | Prospective rating : at baseline ; Retrospective rating : at follow-up (on average,12 weeks after recruitment) | 
| Acceptability outcome 3 : perceived coherence of the intervention (prospective and retrospective) | Rated on an 11-point numerical rating scale (0-10; 10 = better outcome) | Prospective rating : at baseline ; Retrospective rating : at follow-up (on average,12 weeks after recruitment) | 
| Acceptability outcome 4 : perceived effectiveness of the intervention (prospective and retrospective) | Rated on an 11-point numerical rating scale (0-10; 10 = better outcome) | Prospective rating : at baseline ; Retrospective rating : at follow-up (on average,12 weeks after recruitment) | 
| Acceptability outcome 5 : perceived self-efficacy relating to the intervention (prospective and retrospective) | Rated on an 11-point numerical rating scale (0-10; 10 = better outcome) | Prospective rating : at baseline ; Retrospective rating : at follow-up (on average,12 weeks after recruitment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Physical functioning | Measured using the self-reported Brief pain inventory (short form); (0-70; 70 = worse outcome) | From baseline to follow-up (approx 12 weeks) | 
| Change in Pain intensity | Measured using the self-reported Brief pain inventory (short form) (0-40; 40 = worse outcome) | From baseline to follow-up (approx 12 weeks) | 
| Change in Emotional functioning | Measured using the self-reported Profile of mood states (-32 to 200; 200 = worse outcome) | From baseline to follow-up (on average, 12 weeks) | 
| Change in Central sensitization | Measured using the self-reported Central sensitization inventory (0-100; 100=worse outcome) | From baseline to follow-up (on average, 12 weeks) | 
| Change in Symptoms of fibromyalgia | Measured using the self-reported Fibromyalgia impact questionnaire(for the fibromyalgia population only) (0=100; 100 = worse outcome) | From baseline to follow-up (on average, 12 weeks) | 
| Participant ratings of global improvement and satisfaction with treatment | Measured using the self-reported Patient global impression of change (1-7; 7 = better outcome) | Follow-up (on average, 12 weeks after recruitment) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic pain, Reconsolidation therapy, Propranolol, Treatment