CMT1A
Conditions
Keywords
Physical medicine and rehabilitation, Neurology
Brief summary
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.
Interventions
DRUGEllaOne
* 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.
DRUGEllaOne placebo
* 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.
Sponsors
University Hospital, Strasbourg, France
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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 |
Countries
France
Outcome results
None listed