Amitriptyline for Erythromelalgia

(EASE Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called amitriptyline, an antidepressant, to determine if it can reduce pain from erythromelalgia, a condition causing burning pain, redness, and warmth in the hands and feet. Participants will apply either the medication or a placebo to their hands or feet twice daily and record their pain levels. The goal is to determine if the medication can lower the intensity of pain attacks compared to the placebo. Suitable candidates have erythromelalgia with frequent, moderate to severe pain attacks. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that amitriptyline, in the form of ATX01, might be a safe option for treating erythromelalgia. In studies, many patients experienced pain relief using a skin-applied version of amitriptyline combined with another drug, and it was generally well accepted. Other research tested ATX01 for a similar condition and found it to be safe.

Since this trial is in the mid-stage, some evidence already suggests that the treatment is generally safe for people. However, it is still being tested to ensure its effectiveness for erythromelalgia and to check for any rare side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using Amitriptyline for erythromelalgia because it offers a potentially novel approach to treating this painful condition. Unlike the standard treatments, which often include pain relievers or topical medications, Amitriptyline acts as a tricyclic antidepressant, which might help manage nerve-related pain by modulating neurotransmitter pathways. This mechanism could provide relief where other treatments fall short, offering hope for a more effective management option for patients with erythromelalgia.

What evidence suggests that this treatment might be an effective treatment for erythromelalgia?

Research has shown that using amitriptyline as a cream, such as ATX01, might help reduce pain from erythromelalgia, a condition causing severe pain in the hands and feet. In earlier studies, about 75% of patients using a cream with both amitriptyline and ketamine experienced pain relief. This trial will evaluate the effectiveness of ATX01, which contains only amitriptyline, in reducing pain attacks. Although more research is needed to confirm its effectiveness when used alone, early results are promising for those with erythromelalgia. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05917912?cond=erythomelagia&rank=1

EASE (Efficacy of ATX01 Study in Erythromelalgia)

The goal of this two-center, randomized, double-blinded, parallel-group, placebo-controlled clinical study is designed to compare the efficacy of twice daily ...

2.

mayo.edu

mayo.edu/research/clinical-trials/cls-20549518

EASE (Efficacy of ATX01 Study in Erythromelalgia) (EASE)

The purpose of this study is to assess the effectiveness of ATX01 15% compared to placebo in the management of pain attacks due to erythromelalgia.

3.

withpower.com

withpower.com/trial/phase-2-erythromelalgia-5-2023-51057

Amitriptyline for Erythromelalgia · Info for Participants

This trial tests a skin-applied treatment called ATX01 for people with erythromelalgia, a condition causing severe pain in the hands and feet.

4.

mayoclinicproceedings.org

mayoclinicproceedings.org/article/S0025-6196(22)00498-0/fulltext

Erythromelalgia: A Review of Medical Management ...

Several topical medications have been used to address the pain associated with EM. These include lidocaine, amitriptyline in combination with ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12113215/

Comparative Efficacy and Tolerability of Treatments for ...

About 75% of erythromelalgia patients found pain relief with a topical combination of amitriptyline and ketamine, and the treatment was well accepted.

6.

algotx.com

algotx.com/2025/02/18/algotx-announces-results-of-its-phase-2-act-trial-of-atx01-in-chemotherapy-induced-peripheral-neuropathy/

AlgoTx Announces Results of its Phase 2 “ACT” Trial ...

ACT is an international, double-blind, placebo-controlled evaluation of the efficacy and safety of two concentrations of ATX01 in patients suffering from CIPN.