What is the mechanism of action of this treatment?

Common treatments for Erythromelalgia, particularly those involving topical applications like ATX01, often aim to reduce pain intensity by targeting local pain pathways and inflammatory processes. These treatments may work by modulating the activity of small nerve fibers, reducing local inflammation, or altering pain signaling mechanisms. For instance, topical agents can provide localized relief without systemic side effects, making them particularly suitable for managing the intense burning pain and redness characteristic of Erythromelalgia. This approach is crucial for patients as it offers a targeted, often more tolerable, method to manage symptoms and improve quality of life.

What side effects are associated with this type of intervention?

The study on ATX01, a topical application for erythromelalgia, focuses on reducing pain intensity. While specific side effects for ATX01 are not detailed, common side effects for topical treatments in general may include local skin reactions such as redness, itching, or irritation. For systemic treatments of erythromelalgia, side effects can vary widely depending on the medication used, but may include gastrointestinal issues, dizziness, and fatigue. It is important to consult with a healthcare provider to understand the potential side effects of any specific treatment.

What prior FDA approvals exist?

There is limited information available on FDA-approved treatments specifically for Erythromelalgia, particularly those involving topical applications like ATX01. Erythromelalgia is a rare condition, and treatments often focus on symptom management rather than cure. Common approaches include oral medications such as gabapentin, pregabalin, and certain antidepressants, which help manage pain. Topical treatments, while not specifically FDA-approved for Erythromelalgia, may include compounded creams containing lidocaine or capsaicin to provide localized pain relief. Further research and clinical trials, such as the ATX01 study, are essential to establish effective topical treatments for this condition.

What other types of research exist?

Promising novel alternatives to ATX01 for Erythromelalgia patients include small-molecule AT2R antagonists like EMA200 and EMA300, which have shown dose-dependent analgesic efficacy in rat models of neuropathic pain. Additionally, TRPV1 antagonists, such as AMG 517, have demonstrated potential for treating chronic nociceptive and neuropathic pain, although they may have side effects like increased body core temperature. These alternatives could be considered for further investigation and potential use in 2024.

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Tricyclic Antidepressant

Amitriptyline for Erythromelalgia (EASE Trial)

Phase 2

Waitlist Available

Research Sponsored by AlgoTherapeutix

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Documented diagnosis of erythromelalgia, as characterized by redness, warmth, and burning pain of the extremities (most commonly feet), typically precipitated by heat or exercise and relieved by cooling

Mean pain attack intensity, measured on the 11-point NPRS, of ≥4 and ≤9 at baseline and ≥4 pain attacks per week as documented through eDiary use during the 3 weeks prior to randomization (Day -21 to Day -1)

Must not have

Evidence of skin breakdown, ulcers, papules and > +2 pitting edema of the affected limbs

Presence of glaucoma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up during the last 7 full days (day 14 to day 20) of each treatment period

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include those commonly associated with amitriptyline such as drowsiness, dry mouth, blurred vision, constipation and urinary retention. Since this is a topical application, systemic side effects may be less common but can still occur.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have erythromelalgia, with symptoms like redness, warmth, and pain in my feet or hands that worsen with heat or exercise.

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My average pain level is between 4 and 9, and I've had at least 4 pain attacks each week for the last 3 weeks.

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I am not pregnant and will use or am using effective birth control, or I am surgically sterilized or have been menopausal for at least 1 year.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have skin issues and swelling in my limbs.

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I have glaucoma.

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I have trouble emptying my bladder or have a significantly enlarged prostate.

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I have a history of heart artery disease.

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I have had or currently have major depression.

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I haven't taken any medications in the last 24 weeks that affect my heart's rhythm.

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I haven't used opioids in the last 4 weeks or during the study.

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

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I have an implanted device for pain management.

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I haven't taken any drugs that affect liver enzyme CYP2D6 in the last month.

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My body processes some medications slowly.

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I cannot apply medication to my own hands or feet.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ during the last 7 full days (day 14 to day 20) of each treatment period

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~during the last 7 full days (day 14 to day 20) of each treatment period

This trial's timeline: 3 weeks for screening, Varies for treatment, and during the last 7 full days (day 14 to day 20) of each treatment period for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Comparison between Treatments (ATX01 15% vs. Placebo) of mean pain attack intensity score

Secondary study objectives

Change in Beck Depression Inventory (BDI) score.

Change in pain interference with daily life using the Brief Pain Inventory - Short Form questionnaire (BPI-SF)

Change in pain score before and after rescue measures (e.g., cooling).

+4 more

Trial Design

2Treatment groups

Active Control

Group I: Sequence AActive Control2 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 BActive Control2 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

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Erythromelalgia, particularly those involving topical applications like ATX01, often aim to reduce pain intensity by targeting local pain pathways and inflammatory processes. These treatments may work by modulating the activity of small nerve fibers, reducing local inflammation, or altering pain signaling mechanisms. For instance, topical agents can provide localized relief without systemic side effects, making them particularly suitable for managing the intense burning pain and redness characteristic of Erythromelalgia. This approach is crucial for patients as it offers a targeted, often more tolerable, method to manage symptoms and improve quality of life.

Pharmacological activation of AMPK inhibits incision-evoked mechanical hypersensitivity and the development of hyperalgesic priming in mice.Structural determinants of the hyperalgesic activity of myotoxic Lys49-phospholipase A2.High-intensity swimming exercise reduces neuropathic pain in an animal model of complex regional pain syndrome type I: evidence for a role of the adenosinergic system.