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Phase Pilot Trial II-III With N-acetylcysteine in SEPN1- related myopathy (SELNAC)

Study Title
Pharmacological Treatment of a Rare Genetic Disease: Pilot Trial Phase II-III With N-acetylcysteine in Myopathy Associated SEPN1-RM (Selenoprotein N-related Myopathy) (SELNAC)

Study Start: September 2015

Purpose
The aim of this study is to determine whether the administration of N-acetylcysteine (NAC) improves oxidative stress and/or its consequences in SEPN1-related myopathy, a devastating muscle disease with no treatment.

The primary objective of the study is:
  • to determine the ratio of reduced versus oxidized glutathione in blood erythrocytes.
The secondary objectives of the study are to assess:
  • the locomotor functional capacities
  • the lung functional capacity
  • the body mass composition
  • other biochemical and molecular markers in blood samples, muscle and fibroblasts
Study Type: Interventional

Study Description
This is a prospective, monocentric, crossover, double-blind, placebo-controlled study. For each patient, the study will be divided in two treatment periods of 6 months separated by a 2 month washout period. 24 patients will be randomized in two groups, one group is treated first with a placebo during 6 months, followed by 6 months on NAC 2400 mg/day; the second group is treated in the reverse sequence, NAC 2400 mg/day then placebo. 24 healthy volunteers will also be enrolled in the study in order to collect reference values for biochemical biomarkers.
On day 1, patients will be hospitalized to rest and collect information (standardized questionnaires) about lifestyle and environmental factors (diet, physical activity, smoking…) which can influence the redox status and contribute to variability of disease severity. During follow-up visits, we will analyze the impact of NAC treatment on:
  • biochemical and molecular markers which reflect: i) the status of antioxidant defense mechanisms; ii) cell damage due to oxidative stress; iii) redox-related inflammation; and iv) redox-related metabolic alterations
  • measures of locomotor functional capacity
  • body mass composition, in terms of lean mass and fat mass
  • respiratory function including diaphragmatic strength and fatigue
These measures will be compared before and after treatment. They will provide information on the status of oxidative stress and clarify the effects of NAC on the evolution of the disease in these patients. The correlation of biomarker measurements in muscle and systemic tissues (skin fibroblasts, blood) will be checked.

Eligibility
Inclusion Criteria:

  • Males and females 18 to 60 years old
  • Subject has been diagnosed with SEPN1-related myopathy due to homozygous or compound heterozygous mutations in the SEPN1 gene
  • Subject has given informed written consent
  • Subject can be followed up throughout the duration of the study
  • Subject is trained in the use of cough assist
  • Subject has health insurance
  • Subject is committing to not introducing major changes in diet and lifestyle during the study period
Exclusion Criteria:
  • Pregnancy
  • Intolerance to NAC, galactose or fructose; glucose or galactose malabsorption; lactase deficiency
  • Consumption of synthetic vitamins, NAC or other antioxidants within 3 months prior to inclusion
  • Ocasional treatment with corticosteroids or non-steroidal anti-inflammatory drugs in the 4 weeks preceding the inclusion, or for more than 3 days between 12 and 4 weeks prior to inclusion
  • Planned surgery within 3 months before inclusion or during the inclusion period
  • Intercurrent illness: chronic infectious disease (HIV, hepatitis), asthma, malignancy, hematological disease, others
  • Expected survival less than 14 months
  • Inability to understand the instructions or the implications of the protocol
Please refer to this study by its ClinicalTrials.gov identifier: NCT02505087

Study Site
UMR8251 University Paris Diderot / CNRS
Paris, France, 75013
Contact: ANA FERREIRO, MD, PhD

For more information, please contact:

Brigitte ESTOURNET, MD, PhD + 33 (0) 1 47 10 78 90 This e-mail address is being protected from spambots. You need JavaScript enabled to view it
Ana FERREIRO, MD, PhD + 33 (0)1 57 27 79 59 This e-mail address is being protected from spambots. You need JavaScript enabled to view it