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Pharmacological Treatment of a Rare Genetic Disease: N-acetylcysteine in Myopathy Associated Selenoprotein N-related Myopathy (SEPN1-RM) (SelNac)

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ClinicalTrials.gov Identifier: NCT02505087
Recruitment Status : Terminated
First Posted : July 22, 2015
Last Update Posted : September 29, 2020
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE June 25, 2015
First Posted Date  ICMJE July 22, 2015
Last Update Posted Date September 29, 2020
Actual Study Start Date  ICMJE September 2015
Actual Primary Completion Date April 24, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2015)
Ratio of reduced glutathione and oxidized glutathione in blood erythrocytes. [ Time Frame: 6 months in each period ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2015)
  • measure of health status according The 36-Item Short Form Health Survey (SF36) [ Time Frame: 6 months in each crossover period ]
  • Evaluate the impact of fatigue according the Fatigue Severity Scale (FSS) [ Time Frame: 6 months in each crossover period ]
  • Measurement of biomarkers in blood samples, muscle and fibroblasts [ Time Frame: 6 months in each crossover period ]
  • Measure of Activity Limitation (Activlim test) [ Time Frame: 6 months in each crossover period ]
  • Running speed measured by the test of 10 m [ Time Frame: 6 months in each crossover period ]
  • Measures of motor function according a Motor Function Measure scale (MFM ) [ Time Frame: 6 months in each crossover period ]
  • Muscular endurance is measured by the test of 2 minutes walk [ Time Frame: 6 months in each crossover period ]
  • Measurement of the maximum voluntary contraction of the quadriceps [ Time Frame: 6 months in each crossover period ]
  • The measurement of the endurance of the quadriceps [ Time Frame: 6 months in each crossover period ]
  • Assessment of dyspnea according Borg scale [ Time Frame: 6 months in each crossover period ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacological Treatment of a Rare Genetic Disease: N-acetylcysteine in Myopathy Associated Selenoprotein N-related Myopathy (SEPN1-RM)
Official Title  ICMJE Pharmacological Treatment of a Rare Genetic Disease: Pilot Trial Phase II-III With N-acetylcysteine in Myopathy Associated SEPN1-RM (Selenoprotein N-related Myopathy)
Brief Summary The objective of this study is to determine whether the administration of N-acetylcysteine (NAC) improves oxidative stress. To determine this, the study will assess the impact of oral treatment on the balance between reduced and oxidized form of glutathione in erythrocytes of peripheral blood.
Detailed Description

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 treated first with placebo during 6 months, followed by 6 months; the second group treated in the reverse sequence, then placebo.

24 healthy volunteers will also be enrolled in the study in order to collect reference values for biochemical biomarkers.

D-1: run-up visit, patients will be hospitalized in intensive care unit to collect information about diet, physical activity and smoking.

During follow-up visits: we will analyze the impact of treatment with N-acetylcysteine (NAC) on:

  • Biomarkers of redox homeostasis,
  • Measures of locomotor functional capacity,
  • Body mass composition,
  • Respiratory functional abilities.

Biomarkers that reflect the status of antioxidant defense mechanisms, parameters that reflect the cell damage to oxidative stress, the markers of inflammation and metabolic alterations induced by oxidative stress, body composition in terms of lean mass and fat mass, the motor functional abilities, respiratory function capabilities, will be compare before and after treatment.

These measures could complement the information on the status of oxidative stress and clarify the effects of N-acetylcysteine (NAC) on the evolution of the disease in these patients.

The correlation of biomarker measurements in muscle and systemic tissues will be checked.

Furthermore we will collect information about the lifestyle through standardized questionnaires that include diet, smoking, and habitual physical activity. Environmental factors and lifestyle can influence the balance oxidant / antioxidant patients and contribute to the variability of the clinical severity of the disease.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Selenoprotein N-related Myopathy
Intervention  ICMJE
  • Drug: N-Acetylcysteine followed by Placebo

    Arm receiving N-Acetylcysteine (NAC) for 6 months and then placebo for 6 months.

    Treatment periods are separated by a 2 month washout.

  • Drug: Placebo followed by N-Acetylcysteine
    Arm receiving placebo for 6 months then N-acetylcysteine (NAC) for 6 months. Treatment periods are separated by a 2 month washout.
Study Arms  ICMJE
  • Active Comparator: Placebo followed by N-Acetylcysteine
    Arm receiving placebo for 6 months, then N-Acetylcysteine (NAC) for 6 months.
    Intervention: Drug: Placebo followed by N-Acetylcysteine
  • Experimental: N-Acetylcysteine followed by Placebo
    Arm receiving N-Acetylcysteine (NAC) for 6 months and then placebo for 6 months.
    Intervention: Drug: N-Acetylcysteine followed by Placebo
  • No Intervention: Healthy volunteers
    The purpose of this group is to collect reference values for biochemical markers.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 28, 2020)
7
Original Estimated Enrollment  ICMJE
 (submitted: July 20, 2015)
48
Actual Study Completion Date  ICMJE August 31, 2020
Actual Primary Completion Date April 24, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. For patients:

    • Patient >18 and <60 years old
    • Patients with Selenoprotein N-related myopathy with homozygous or compound heterozygous mutations in the gene SEPN1-RM
    • Informed written consent
    • Patients capable of being followed up throughout the duration of the study
    • Patient trained in the use of cough assist
    • Patients having an health insurance
    • Patient accepting to commit not to introduce major changes in diet and lifestyle during the study period
  2. For healthy volunteers:

    • volunteers >18 and <60 years old
    • Informed written consent
    • Health insurance

Exclusion Criteria:

  1. For patients:

    • Pregnancy
    • Intolerance to N-acetylcysteine (NAC), galactose or fructose; malabsorption glucose or galactose; lactase deficiency
    • Consumption of synthetic vitamins, NAC and other antioxidants within 3 months prior to inclusion
    • Treatment with corticosteroids or non-steroidal anti-inflammatory from time to time in the 4 weeks preceding the inclusion or for more than 3 days between 12 and 4 weeks before inclusion
    • Planned surgery within 3 months before inclusion or during the inclusion period
    • Intercurrent or existing illnesses such as chronic infectious diseases (HIV, hepatitis, etc.), asthma, malignant tumor pathology, Hematological Pathology
    • Expected survival less than 14 months
    • Inability to understand the instructions or the implications of the Protocol
  2. For healthy volunteers:

    • Pregnancy
    • Consumption of synthetic vitamins, NAC and other antioxidants within 3 months prior to inclusion
    • Treatment with corticosteroids or non-steroidal anti-inflammatory from time to time in the 4 weeks preceding the inclusion or for more than 3 days between 12 and 4 weeks before inclusion
    • Planned surgery within 3 months before inclusion or during the inclusion period
    • Intercurrent or existing illnesses such as chronic infectious diseases (HIV, hepatitis, etc.), asthma, malignant tumor pathology, Hematological Pathology
    • Inability to understand the instructions or the implications of the Protocol
    • Bleeding disorders or other bleeding risks or risk of infection.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02505087
Other Study ID Numbers  ICMJE P100152
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Brigitte ESTOURNET, MD, PhD Neuro-Respiratory Rehabilitation Service, Raymond Poincaré Hospital, 92380 Garches, France
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP