Evaluation of the Improvement of Quality of Life of Patients Suffering From Hailey Hailey or Darier Disease After Injections of Botulism Toxin Into Large Folds. (ToxHD)

Evaluation of the Improvement of Quality of Life of Patients Suffering From Hailey Hailey or Darier Disease After Injections of Botulism Toxin Into Large Folds. Toxin Hailey Darier

Hailey Hailey and Darier disease are rare genetic dermatoses. Mutations of 2 genes (ATP2C1 or ATP2A2 respectively) are responsible for the diseases. These genes have a key role in calcium pump; their defect create abnormal link between keratinocytes' desmosomes and induce skin lesions. Clinically, patients present with inflammatory lesions located in the folds. Quality of life is impaired because of pain, pruritus and tendency to infections. Lesions are permanent but acute exacerbations occur in hot seasons because of increased sweating. Usual therapies are often not effective (local treatment, laser, phototherapy). Because sweating is a well established inducing or aggravating factor, botulism toxin could be an effective treatment for these diseases.

Botulism toxin is already used in clinical practice and acts via a decreased sweet secretion. Improvement of skin lesions in Hailey-Hailey or Darier diseases has been previously reported in a few cases but there is no study properly evaluating the benefit of such treatment.

The aim of the project is to study the improvement of quality of life for patients suffering from Hailey-Hailey or Darier diseases after a injections of botulism toxin in large skin folds. The principal objective is to estimate the distribution of the variation of quality of life at M1 vs. baseline.

Study Overview

• Status: Completed
• Conditions: Darier Disease; Hailey-Hailey Disease
• Intervention / Treatment: Drug: Botulism Toxin Treatment

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis (clinical and histological features) of Hailey Hailey or Darier diseases.
• Moderate to very severe lesions located in large folds
• Patient aged 18 ans or more
• Patient with health coverage
• Patient who have signed the consent form
• Patient proficient into filling out the questionnaires.

Exclusion Criteria:

• Hypersensibility to toxin or excipients
• Myastheny
• Deglutition's problems
• Past medical history of dysphagia or aspiration pneumonia
• Pregnancy (positive B-HCG test performed a maxima 72h before) or breastfeeding
• Mental , physical incapacity to fill in the questionnaires
• Guardianship patients
• Skin infections at the inclusion visit
• Application in the last 7 days at the site of injection of local treatments (apart emollients or antiseptics) or injections of botulism toxin or dynamic phototherapy or laser in the last 6 months.
• Systemic treatment with aminosides in the last 15 days
• Inclusion in another study in the last 2 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botulism Toxin treatment; Injection of 50 UI Botulism toxin for the treated zone	Drug: Botulism Toxin Treatment; Injection of 50 UI of botulism toxin for treated zone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of quality of life measured by change in the DLQI score	Variation of DLQI score between Baseline and M1	Day 0 and day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of quality of life measured by change in the DLQI score	Variation of DLQI score between Baseline and M3	Day 0 and day 90
Evaluation of quality of life measured by change in the DLQI score	Variation of DLQI score between Baseline and M6	Day 0 and day 180
Evaluation of skin improvement in treated areas using change the IGA score	Variation of IGA score between Baseline and M1	Day 0 and Day 30
Evaluation of skin improvement in treated areas using change the IGA score	Variation of IGA score between Baseline and M3	Day 0 and Day 90
Evaluation of skin improvement in treated areas using change the IGA score	Variation of IGA score between Baseline and M6	Day 0 and Day 180
Evaluation of psychosocial impairment at measured by change in the HidroQoL score	Variation of HidroQoL score between Baseline and M1	Day 0 and Day 30
Evaluation of psychosocial impairment measured by change in the HidroQoL score	Variation of HidroQoL score between Baseline and M3	Day 0 and Day 90
Evaluation of psychosocial impairment measured by change in the HidroQoL score	Variation of HidroQoL score between Baseline and M6	Day 0 and Day 180
Evaluation by the investigator of the treated lesions global severity change as assessed by comparison using measurement of the affected area	Variation of treated lesions severity between Baseline and M1	Day 0 and Day 30
Evaluation by the investigator of the treated lesions global severity change as assessed by comparison using measurement of the affected area	Variation of treated lesions severity between Baseline and M3	Day 0 and Day 90
Evaluation by the investigator of the treated lesions global severity change as assessed by comparison using measurement of the affected area	Variation of treated lesions severity between Baseline and M6	Day 0 and Day 180
Evaluation of patient's satisfaction Using the IGA score " Improvement Global Assessment "		Day 180
Evaluation of patient treatment acceptability using visual analogic pain scale		Day 0 after injection
Evaluation of acceptability over the medium to long term as assessed by occurence of side effects		Day 30
Evaluation of acceptability over the medium to long term as assessed by occurence of side effects		Day 90
Evaluation of acceptability over the medium to long term as assessed by occurence of side effects		Day 180
Evaluation of long term efficacy as assessed by percentage of non-responder patients with IGA score egal to 0		Day 30
Evaluation of long term efficacy as assessed by delay for significant relapse (reappearance of skin lesions justifying treatment)		Up to 180 days
Evaluation of long term efficacy as assessed by comparison between the number of infection episodes occurred during the 6 months before the study or during the 6 months of the study		Up to 180 days

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Aude MAZA RIOLAND, MD, University Hospital, Toulouse

Publications and helpful links

General Publications

• Dreyfus I, Maza A, Rodriguez L, Merlos M, Texier H, Rousseau V, Sommet A, Mazereeuw-Hautier J. Botulinum toxin injections as an effective treatment for patients with intertriginous Hailey-Hailey or Darier disease: an open-label 6-month pilot interventional study. Orphanet J Rare Dis. 2021 Feb 18;16(1):93. doi: 10.1186/s13023-021-01710-x.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: May 20, 2016
• First Submitted That Met QC Criteria: May 20, 2016
• First Posted (Estimate): May 25, 2016

Study Record Updates

• Last Update Posted (Actual): December 13, 2021
• Last Update Submitted That Met QC Criteria: November 29, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Botulism Toxin
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Skin Diseases; Infections; Genetic Diseases, Inborn; Neuromuscular Diseases; Foodborne Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Skin Diseases, Genetic; Skin Diseases, Vesiculobullous; Neuromuscular Junction Diseases; Clostridium Infections; Poisoning; Keratosis; Neurotoxicity Syndromes; Darier Disease; Botulism; Pemphigus, Benign Familial; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Botulinum Toxins
• Other Study ID Numbers: 14 7316 02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided