Ulipristal Acetate In Disease Charcot-Marie-Tooth Type of 1A

Study Overview
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Brief Summary
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The disease Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy, for which no treatment has proved its effectiveness. It is autosomal dominant, associated with a duplication of the chromosome 17p11.2 region which leads to overexpression of the gene and the protein-peripheral myelin protein-22 (PMP22), a major component of peripheral myelin. In animals and humans, PMP22 mRNA level of glutathione S-transferase theta 2 and Cathepsin A (markers of oxidative stress), detected in a skin biopsy are markers that may play a role in the prognosis evolution of the disease. Furthermore, several studies have shown that the administration of progesterone increased the expression of PMP22 gene (measured in a skin biopsy) and worsening symptoms. In contrast, anti-progestins reduce the synthesis of PMP22 and improve symptoms in rat CMT1A. The long-term safety of anti-progesterone was evaluated for mifepristone (RU486) ulipristal acetate and (EllaOne®). Few side effects have been reported including a few cases of endometrial hyperplasia reversible upon discontinuation of treatment. With the RU486, rare cases of adrenal androgen and failure have been observed. However, EllaOne® has low antagonistic action on the glucocorticoid receptor and no action on androgen receptors. The investigators therefore believe that it will be well tolerated in humans and will reduce the synthesis of PMP22 and the action of oxidative stress by improving disability of patients.

Official Title
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LONG-TERM EFFECTS TOLERANCE AND THE Ulipristal Acetate IN DISEASE Charcot-MARIE-TOOTH TYPE OF 1A

Conditions
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CMT1A

Intervention / Treatment
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* Drug: EllaOne
* Drug: EllaOne placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male 18-70 years CMT1A proven genetically (17p11.2 duplication) symptomatic CMT1A (MRC score <5 in at least one muscle group) Non severe axonal impairment (amplitude of the motor evoked potential on the median nerve and / or ulnar than 50% of normal) Subject contacted with a valid phone number Subject affiliated to a social security scheme Subject has been informed of the results of the medical examination prior Exclusion Criteria: Another cause of neuropathy: Chronic alcohol intoxication, chemotherapy, diabetes, kidney failure, monoclonal gammopathy, cryoglobulin, B12 deficiency, hepatitis B / C, HIV, Lyme or poliomyelitis Liver failure Lapp lactase deficiency, malabsoprtion syndrome glucose / galactose Support long-term drug interacting with the CYP3A4 Patients with indication against xylocaine adrenaline In the biopsy site: surgery, skin disease or local infection Immunosuppression innate or acquired Hypersensitivity to the active substance / excipient uncontrolled severe asthma Treatment with vitamin C or vitamin B3 in the four weeks preceding randomization Orthopaedic surgery of the lower limbs in the 6 months prior to randomization or planned Against indication xylocaine adrenaline Malfunction of the innate or acquired coagulation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Arm (1) will be randomised to receive either : 5 mg/per os of EllaOne every day through 12 months. 10 mg/per os of EllaOne every day through 12 months. EllaOne placebo/per os every day through 12 months. | Drug: EllaOne<br>* 5 mg/per os of EllaOne every day through 12 months. 10 mg/per os of EllaOne every day through 12 months. EllaOne placebo/per os every day through 12 months.<br>* Other names: 3: Experimental;Drug: EllaOne placebo<br>* 5 mg/per os of EllaOne every day through 12 months. 10 mg/per os of EllaOne every day through 12 months. EllaOne placebo/per os every day through 12 months.<br>* Other names: 3: Experimental;|
| Experimental: 2<br>Arm (2) will be randomised to receive either : 5 mg/per os of EllaOne every day through 12 months. 10 mg/per os of EllaOne every day through 12 months. EllaOne placebo/per os every day through 12 months. | Drug: EllaOne<br>* 5 mg/per os of EllaOne every day through 12 months. 10 mg/per os of EllaOne every day through 12 months. EllaOne placebo/per os every day through 12 months.<br>* Other names: 3: Experimental;Drug: EllaOne placebo<br>* 5 mg/per os of EllaOne every day through 12 months. 10 mg/per os of EllaOne every day through 12 months. EllaOne placebo/per os every day through 12 months.<br>* Other names: 3: Experimental;|
| Experimental: 3<br>Arm (3) will be randomised to receive either : 5 mg/per os of EllaOne every day through 12 months. 10 mg/per os of EllaOne every day through 12 months. EllaOne placebo/per os every day through 12 months. | Drug: EllaOne<br>* 5 mg/per os of EllaOne every day through 12 months. 10 mg/per os of EllaOne every day through 12 months. EllaOne placebo/per os every day through 12 months.<br>* Other names: 3: Experimental;Drug: EllaOne placebo<br>* 5 mg/per os of EllaOne every day through 12 months. 10 mg/per os of EllaOne every day through 12 months. EllaOne placebo/per os every day through 12 months.<br>* Other names: 3: Experimental;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of the effectiveness of Ellaone. This will be assessed by the production of RNA PMP22 using skin biopsy. |  | 12 months after treatment with EllaOne | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Physical medicine and rehabilitation, Neurology