Amitriptyline for Erythromelalgia

(EASE Trial)

Recruiting at 1 trial location

Overseen By AlgoTherapeutix

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AlgoTherapeutix

Must not be taking: Antiarrhythmics, Antidepressants, Antipsychotics, others

Disqualifiers: Glaucoma, Urinary retention, Coronary artery disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a skin-applied treatment called ATX01 for people with erythromelalgia, a condition causing severe pain in the hands and feet. Participants will use the treatment twice daily to see if it reduces their pain.

Will I have to stop taking my current medications?

The trial allows you to continue taking your current medications as long as they are not topical agents applied to the hands or feet, and the dose has been stable for at least 4 weeks before the study. However, certain medications that affect heart rhythm, opioids, and some other specific drugs must be stopped before joining the trial.

What evidence supports the effectiveness of the drug amitriptyline for treating erythromelalgia?

Amitriptyline has shown effectiveness in reducing pain and improving well-being in conditions like fibrositis and fibromyalgia, suggesting it might help with pain management in erythromelalgia as well. ^{1 2 3 4 5}

Is amitriptyline generally safe for humans?

The safety data for amitriptyline is not clearly detailed in the studies, but it has been used in various trials for conditions like fibromyalgia. Some patients discontinued it due to lack of effectiveness rather than side effects, suggesting it is generally tolerated, but more research is needed to confirm its long-term safety. ^{1 3 6 7 8}

How does the drug amitriptyline differ from other treatments for erythromelalgia?

Amitriptyline is unique because it is a tricyclic antidepressant that has shown effectiveness in treating various types of chronic pain, including fibromyalgia and migraines, by mechanisms that are independent of its antidepressant effects. This suggests it may offer pain relief for erythromelalgia, a condition with limited standard treatment options, through a different pathway than typical pain medications. ^{1 3 9 10 11}

Eligibility Criteria

Adults with erythromelalgia, experiencing redness, warmth, and burning pain in extremities triggered by heat or exercise. They must have a documented diagnosis, an average pain intensity of 4-9 on the NPRS scale, at least four attacks per week, stable medication doses for four weeks prior to the study (except topical agents), and agree to contraception if applicable.

Inclusion Criteria

Patients having signed a written informed consent prior to any study related procedure

My medication doses have been stable for 4 weeks and will remain the same during the study.

I agree to use two forms of birth control if I'm sexually active with a woman who can have children, and not to donate sperm for 90 days after my last dose.

Exclusion Criteria

The doctor thinks the patient may be at risk of hurting themselves, based on a talk with the patient and a special scale used to check for this.

I am taking more than 2 painkillers from different classes along with the study drug.

I haven't used any medical creams on my arms or legs, except for cosmetic reasons, in the last 12 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants undergo a baseline period to establish initial conditions

3 weeks

Treatment Period 1

Participants receive either ATX01 or placebo for 3 weeks

3 weeks

Daily applications

Wash-out

Participants undergo a wash-out period to clear previous treatment effects

3 weeks

Treatment Period 2

Participants receive the alternate treatment (ATX01 or placebo) for 3 weeks

3 weeks

Daily applications

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Amitriptyline Hydrochloride
• Placebo

Trial Overview The EASE trial is testing ATX01 (Amitriptyline Hydrochloride) cream against a placebo. Participants will apply it twice daily to their feet/hands over two 3-week periods while tracking pain attack intensity using an eDiary. The main goal is to see if ATX01 reduces the severity of pain attacks more effectively than a placebo.

Participant Groups

Group I: Sequence A Active Control 2 Interventions

i)screening and randomization; ii) baseline period (3 weeks); iii) treatment period 1 with placebo(3 weeks); iv) wash-out period (3 weeks); v), treatment period 2 with ATX-01(3 weeks); vi) follow-up visit

Group II: Sequence B Active Control 2 Interventions

i)screening and randomization; ii) baseline period (3 weeks); iii) treatment period 1 with ATX-01(3 weeks); iv) wash-out period (3 weeks); v), treatment period 2 with placebo (3 weeks); vi) follow-up visit

Who Is Running the Clinical Trial?

AlgoTherapeutix

Lead Sponsor

Trials

2

Recruited

290+

Findings from Research

In a 12-week double-blind crossover study involving 52 patients with chronic pain, amitriptyline showed a subjective reduction in pain at 2 and 4 weeks compared to placebo, but this effect did not persist at 6 weeks.

Overall, there were no significant differences in global improvement between amitriptyline and placebo, and 20 patients withdrew from the study before completion, indicating potential challenges in treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled study of amitriptyline in the treatment of chronic pain. Pilowsky, I., Hallett, EC., Bassett, DL., et al.[2021]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Improvements in pain responsiveness in patients with fibrositis after successful treatment with amitriptyline. [2013]

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

A controlled study of amitriptyline in the treatment of chronic pain. [2021]

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

Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. [2018]

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

Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. A randomized, double-blind clinical trial. [2019]

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

Trial of amitriptyline for relief of pain in amputees: results of a randomized controlled study. [2022]

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

Analgesic Medication in Fibromyalgia Patients: A Cross-Sectional Study. [2022]

7. Canada pubmed.ncbi.nlm.nih.gov

Clinical usefulness of amitriptyline in fibromyalgia: the results of 23 N-of-1 randomized controlled trials. [2015]

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

Amitriptyline for musculoskeletal complaints: a systematic review. [2018]

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

Low dose amitriptyline in the treatment of chronic pain. [2022]

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

Amitriptyline in migraine prophylaxis. [2019]

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

The analgesic effect of amitriptyline on chronic facial pain. [2022]