Reconsolidation Therapy With Propranolol as a Treatment for Chronic Pain

Fibromyalgia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05085782
• Other study ID #: 2022-4092
• Status: Recruiting
• Phase: Phase 2
• Start date: February 7, 2022
• Est. completion date: September 2025

Study information

• Verified date: May 2023
• Source: Université de Sherbrooke
• Contact: Guillaume Leonard, PhD
• Phone: 819-780-2220
• Email: guillaumne.leonard2[@]usherbrooke.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: September 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Low-back Pain
• Chronic Pain
• Fibromyalgia
• Low Back Pain

Intervention

Drug:
• Propranolol Hydrochloride
6 weekly doses (40 to 80 mg) 1h before the reactivation procedure
• Placebo
6 weekly doses (40 to 80 mg) 1h before the reactivation procedure

Behavioral:
• Reactivation procedure
Description/visualization of painful movements/activities
• Pain neuroscience education
In the form of 10 videos that participants will watch on their own time

Locations

Country	Name	City	State
Canada	Centre de recherche sur le vieillissement (CdRV)	Sherbrooke	Quebec
Canada	CRCHUS: Centre de recherche du centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Université de Sherbrooke

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)