Clinical trial NCT02600286: Ulipristal Acetate In Disease Charcot-Marie-Tooth Type of 1A
Official title: LONG-TERM EFFECTS TOLERANCE AND THE Ulipristal Acetate IN DISEASE Charcot-MARIE-TOOTH TYPE OF 1A
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: CMT1A
Keywords: Physical medicine and rehabilitation
Neurology
Lead sponsor: University Hospital, Strasbourg, France
Sponsor class: OTHER
First posted: 2015-11-09
Enrollment: 23
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Analysis of the effectiveness of Ellaone. This will be assessed by the production of RNA PMP22 using skin biopsy.
timeFrame: 12 months after treatment with EllaOne
Secondary outcomes:
Other outcomes:
Locations:
city: Besançon
country: France
facility: Service d'Explorations et pathologies neuro- musculaires
city: Dijon
country: France
facility: Département de Neurologie
city: Nancy
country: France
facility: Département de Neurologie
city: Paris
country: France
facility: Unité de pathologie neuro-musculaire
city: Strasbourg
country: France
facility: Département de Neurologie Centre de Référence des Maladies Neuromusculaires Grand Est (CERNEST) Hôpital de Hautepierre
Study officials:
affiliation: University Hospital, Strasbourg, France
name: Andoni Echaniz-Laguna, MD
role: STUDY_DIRECTOR
affiliation: University Hospital, Strasbourg, France
name: Nicolas Collongues, MD
role: PRINCIPAL_INVESTIGATOR
References: