Reconsolidation Therapy With Propranolol as a Treatment for Chronic Pain

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Low-back Pain; Fibromyalgia
• Intervention / Treatment: Drug: Propranolol Hydrochloride; Behavioral: Reactivation procedure; Behavioral: Pain neuroscience education; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 4C4
      • Centre de recherche sur le vieillissement (CdRV)
    • Sherbrooke, Quebec, Canada, J1H5N4
      • CRCHUS: Centre de recherche du centre hospitalier universitaire de Sherbrooke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Propranolol; 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; 6 weekly doses (40 to 80 mg) 1h before the reactivation procedure; Other Names: Experimental group; Behavioral: Reactivation procedure; Description/visualization of painful movements/activities; Behavioral: Pain neuroscience education; In the form of 10 videos that participants will watch on their own time
Placebo Comparator: Placebo; 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.	Behavioral: Reactivation procedure; Description/visualization of painful movements/activities; Behavioral: Pain neuroscience education; In the form of 10 videos that participants will watch on their own time; Drug: Placebo; 6 weekly doses (40 to 80 mg) 1h before the reactivation procedure; Other Names: Control group

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)

Collaborators and Investigators

• Sponsor: Université de Sherbrooke
• Investigators: Principal Investigator: Guillaume Léonard, PhD, Université de Sherbrooke

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2022
• Primary Completion (Actual): December 30, 2024
• Study Completion (Actual): August 31, 2025

Study Registration Dates

• First Submitted: September 27, 2021
• First Submitted That Met QC Criteria: October 7, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Estimated): September 26, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Treatment; Chronic pain; Propranolol; Reconsolidation therapy
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Rheumatic Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Fibromyalgia; Chronic Pain; Organic Chemicals; Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods; Hydrocarbons; Hydrocarbons, Cyclic; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Amines; Alcohols; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Propanols; Propranolol; Control Groups
• Other Study ID Numbers: 2022-4092

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No