Propranolol Reconsolidation Therapy for Chronic Pain

Recruiting at 1 trial location

Overseen By Guillaume Leonard, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Université de Sherbrooke

Must be taking: Propranolol

Disqualifiers: Neurological, Psychiatric, Recent surgery, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

48 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications that should not be combined with propranolol.

What data supports the effectiveness of the drug propranolol for chronic pain?

The research shows that propranolol, particularly in its long-acting form, is effective for conditions like angina, hypertension, and hyperthyroidism, suggesting it can maintain stable drug levels in the body. This stability might be beneficial for managing chronic conditions, although direct evidence for chronic pain is not provided. ^{1 2 3 4 5}

Is propranolol generally safe for humans?

Propranolol, a medication used for conditions like high blood pressure and heart issues, can cause some side effects, including a rare allergic reaction called serum sickness-like syndrome. It is important for people with a history of drug allergies to be cautious and seek medical attention if they experience unusual symptoms. ^{1 4 6 7 8}

How is the drug propranolol used in reconsolidation therapy for chronic pain different from other treatments?

Propranolol reconsolidation therapy for chronic pain is unique because it targets the reconsolidation process of memories, potentially altering how pain is perceived by disrupting the memory of pain itself. This approach is different from typical pain treatments that focus on directly reducing pain symptoms or inflammation. ^{1 2 9 10 11}

Research Team

Guillaume Leonard, PhD

Principal Investigator

Université de Sherbrooke

Eligibility Criteria

This trial is for French-speaking adults who have been experiencing chronic low back pain or fibromyalgia with an average pain level of at least 4 out of 10 for more than six months. Participants should show signs of central sensitization. Those with severe neurological/psychiatric conditions, health issues that conflict with propranolol use, recent lower-back surgery, or involved in litigation due to their pain cannot join.

Inclusion Criteria

I speak French.

I have been diagnosed with central sensitization.

I have had chronic low back pain or fibromyalgia for over 6 months.

Exclusion Criteria

I am involved in a lawsuit related to my pain condition.

You have a serious mental or neurological condition that is not well controlled, such as severe anxiety or substance abuse.

I am not taking any medication that cannot be combined with propranolol.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 months

Treatment

Participants receive pain neuroscience education and reconsolidation therapy with propranolol or placebo over 6 weekly sessions

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Pain neuroscience education
• Placebo
• Propranolol Hydrochloride
• Reactivation procedure

Trial Overview The study tests the combination of pain neuroscience education and reconsolidation therapy using Propranolol Hydrochloride against a placebo to see if it's feasible and acceptable for treating chronic pain. The impact on patients' pain and function will be measured one month after treatment.

Participant Groups

Group I: Propranolol Experimental Treatment 3 Interventions

1. Pain neuroscience education (10 short videos - 2 to 4 mins each) 2. 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.

Group II: Placebo Placebo Group 3 Interventions

1. Pain neuroscience education (10 short videos - 2 to 4 mins each) 2. 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.

Propranolol Hydrochloride is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Inderal for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Performance anxiety

Approved in European Union as Inderal for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Performance anxiety

Approved in Canada as Inderal for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Performance anxiety

Who Is Running the Clinical Trial?

Université de Sherbrooke

Lead Sponsor

Trials

317

Recruited

79,300+

Findings from Research

Long-acting propranolol (Inderal LA) provides a controlled release of the medication, maintaining higher plasma concentrations over 24 hours compared to conventional tablets, which helps ensure consistent beta-adrenoceptor blockade.

This formulation is equally effective for treating conditions like angina pectoris, hypertension, and hyperthyroidism, while potentially improving patient adherence to treatment due to simplified dosing regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use. Mishriki, AA., Weidler, DJ.[2019]

In a study involving 13 patients undergoing 15 abdominal surgeries, continuous intravenous infusion of propranolol was safely maintained postoperatively, with no complications related to beta-blockade observed.

The average dose required to achieve therapeutic serum levels was 3.0 mg/hr, suggesting that this method could be beneficial in other critical situations where oral medication is not feasible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous propranolol infusion following abdominal surgery. Smulyan, H., Weinberg, SE., Howanitz, PJ.[2016]

The study found that the in-vitro release of propranolol from controlled-release beads followed zero-order kinetics, indicating a consistent release rate over time, which is beneficial for maintaining stable drug levels in the body.

Pharmacokinetic analysis showed that the experimental extended-release formulations had superior bioavailability compared to the marketed Inderal LA formulation, with no evidence of dose-dumping, ensuring safe and effective drug delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability and in-vitro/in-vivo correlation for propranolol hydrochloride extended-release bead products prepared using aqueous polymeric dispersions. Rekhi, GS., Jambhekar, SS.[2019]

A study involving six healthy adult volunteers tested four different brands of propranolol (Inderal, Ciplar, Corbeta, and Propal) to assess variations in how the body absorbs and responds to the medication.

The results showed no significant differences in the pharmacokinetic (how the drug is processed in the body) and pharmacodynamic (the drug's effects on the body) parameters among the brands, indicating they are likely interchangeable in terms of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. Biswas, NR., Garg, SK., Kumar, N., et al.[2013]

In a study involving 12 patients with moderately severe angina pectoris, both conventional propranolol and Inderal L.A. showed similar therapeutic effectiveness in improving exercise tolerance, with no significant differences observed at various time points after dosing.

Patient compliance was high for both treatments, and no serious side effects were reported, indicating that both forms of propranolol are safe and well-accepted by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of propranolol and inderal L.A. in patients with angina. Scott, ME., Balnave, K.[2018]

The study analyzed data from the Canadian Adverse Drug Reaction Monitoring Program to assess the potential link between propranolol hydrochloride and bradycardia, finding that the signals for bradycardia were not statistically significant despite some high calculated statistics.

Although the results did not confirm a strong association between propranolol and bradycardia, the authors suggest that further investigation using larger databases is warranted due to the observed trends.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride. Gavali, DK., Kulkarni, KS., Kumar, A., et al.[2021]

In a study of 102 patients with coronary artery disease, abrupt withdrawal of propranolol did not lead to significant adverse outcomes, with only one myocardial infarction and one change in pain pattern reported in the withdrawal group.

The findings suggest that propranolol rebound effects are infrequent in hospitalized patients, indicating that sudden discontinuation may be safer than previously thought for patients with reduced activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol rebound--a retrospective study. Shiroff, RA., Mathis, J., Zelis, R., et al.[2019]

A 38-year-old woman developed a serum sickness-like syndrome after taking propranolol for four days, highlighting a potential allergic reaction to the medication.

The condition resolved after stopping propranolol and administering prednisone, suggesting that patients with a history of drug allergies should be prescribed beta-blockers with caution, and they should be aware of the rare but serious risk of this syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum sickness-like syndrome associated with propranolol therapy. Yen, MC., Piszczek, JE., Mintzer, DL.[2019]

Controlled-release formulations of propranolol, specifically Elanol and Inderal LA, provide smoother serum level profiles and delayed peak times compared to conventional propranolol, indicating a potentially more stable therapeutic effect.

Elanol showed greater bioavailability than Inderal LA, suggesting that long-acting formulations can be effective without the drawbacks of reduced bioavailability due to first-pass metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations. Perucca, E., Grimaldi, R., Gatti, G., et al.[2019]

In a study involving 70 abstinent heroin addicts, the administration of propranolol before memory retrieval significantly impaired the reconsolidation of drug-related memories, suggesting a potential therapeutic approach for addressing drug-related memories.

The effects of propranolol were specific to drug-related positive and negative memories, indicating that it may help in reducing the emotional impact of these memories in individuals recovering from heroin addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of β-adrenergic receptor blockade on drug-related memory reconsolidation in abstinent heroin addicts. Zhao, LY., Sun, LL., Shi, J., et al.[2013]

In a study involving 10 patients with chronic intermittent claudication, neither propranolol nor metoprolol showed any improvement in the time to first claudication pain compared to a placebo.

Both beta-blockers were ineffective in reducing claudication pain during treadmill tests, indicating they may not be beneficial for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of influence of propranolol and metoprolol on walking distance in patients with chronic intermittent claudication. Bogaert, MG., Clement, DL.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Continuous propranolol infusion following abdominal surgery. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Bioavailability and in-vitro/in-vivo correlation for propranolol hydrochloride extended-release bead products prepared using aqueous polymeric dispersions. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. [2013]

5. Northern Ireland pubmed.ncbi.nlm.nih.gov

Comparison of propranolol and inderal L.A. in patients with angina. [2018]

6. India pubmed.ncbi.nlm.nih.gov

Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Propranolol rebound--a retrospective study. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Serum sickness-like syndrome associated with propranolol therapy. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations. [2019]

10. Ireland pubmed.ncbi.nlm.nih.gov

Effects of β-adrenergic receptor blockade on drug-related memory reconsolidation in abstinent heroin addicts. [2013]

11. England pubmed.ncbi.nlm.nih.gov

Lack of influence of propranolol and metoprolol on walking distance in patients with chronic intermittent claudication. [2019]