Back to resultsPharmacological Treatment of a Rare Genetic Disease: N-acetylcysteine in Myopathy Associated Selenoprotein N-related Myopathy (SEPN1-RM) (SelNac)
Primary Purpose
Selenoprotein N-related Myopathy
Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
N-Acetylcysteine followed by Placebo
Placebo followed by N-Acetylcysteine
Sponsored by
About this trial
This is an interventional treatment trial for Selenoprotein N-related Myopathy focused on measuring Selenoprotein N-related myopathy, biomarkers, washout, N-ACETYLCYSTEINE
Eligibility Criteria
Inclusion Criteria:
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
For healthy volunteers:
- volunteers >18 and <60 years old
- Informed written consent
- Health insurance
Exclusion Criteria:
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
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.
Sites / Locations
- UMR8251 University Paris Diderot / CNRS
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
No Intervention
Arm Label
Placebo followed by N-Acetylcysteine
N-Acetylcysteine followed by Placebo
Healthy volunteers
Arm Description
Arm receiving placebo for 6 months, then N-Acetylcysteine (NAC) for 6 months.
Arm receiving N-Acetylcysteine (NAC) for 6 months and then placebo for 6 months.
The purpose of this group is to collect reference values for biochemical markers.
Outcomes
Primary Outcome Measures
Ratio of reduced glutathione and oxidized glutathione in blood erythrocytes.
Secondary Outcome Measures
measure of health status according The 36-Item Short Form Health Survey (SF36)
Evaluate the impact of fatigue according the Fatigue Severity Scale (FSS)
Measurement of biomarkers in blood samples, muscle and fibroblasts
Measure of Activity Limitation (Activlim test)
Running speed measured by the test of 10 m
Measures of motor function according a Motor Function Measure scale (MFM )
Muscular endurance is measured by the test of 2 minutes walk
Measurement of the maximum voluntary contraction of the quadriceps
The measurement of the endurance of the quadriceps
Assessment of dyspnea according Borg scale
Full Information
NCT ID
NCT02505087
First Posted
June 25, 2015
Last Updated
September 28, 2020
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT02505087
Brief Title
Pharmacological Treatment of a Rare Genetic Disease: N-acetylcysteine in Myopathy Associated Selenoprotein N-related Myopathy (SEPN1-RM)
Acronym
SelNac
Official 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)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Terminated
Study Start Date
September 2015 (Actual)
Primary Completion Date
April 24, 2018 (Actual)
Study Completion Date
August 31, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Selenoprotein N-related Myopathy
Keywords
Selenoprotein N-related myopathy, biomarkers, washout, N-ACETYLCYSTEINE
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo followed by N-Acetylcysteine
Arm Type
Active Comparator
Arm Description
Arm receiving placebo for 6 months, then N-Acetylcysteine (NAC) for 6 months.
Arm Title
N-Acetylcysteine followed by Placebo
Arm Type
Experimental
Arm Description
Arm receiving N-Acetylcysteine (NAC) for 6 months and then placebo for 6 months.
Arm Title
Healthy volunteers
Arm Type
No Intervention
Arm Description
The purpose of this group is to collect reference values for biochemical markers.
Intervention Type
Drug
Intervention Name(s)
N-Acetylcysteine followed by Placebo
Intervention Description
Arm receiving N-Acetylcysteine (NAC) for 6 months and then placebo for 6 months.
Treatment periods are separated by a 2 month washout.
Intervention Type
Drug
Intervention Name(s)
Placebo followed by N-Acetylcysteine
Intervention Description
Arm receiving placebo for 6 months then N-acetylcysteine (NAC) for 6 months. Treatment periods are separated by a 2 month washout.
Primary Outcome Measure Information:
Title
Ratio of reduced glutathione and oxidized glutathione in blood erythrocytes.
Time Frame
6 months in each period
Secondary Outcome Measure Information:
Title
measure of health status according The 36-Item Short Form Health Survey (SF36)
Time Frame
6 months in each crossover period
Title
Evaluate the impact of fatigue according the Fatigue Severity Scale (FSS)
Time Frame
6 months in each crossover period
Title
Measurement of biomarkers in blood samples, muscle and fibroblasts
Time Frame
6 months in each crossover period
Title
Measure of Activity Limitation (Activlim test)
Time Frame
6 months in each crossover period
Title
Running speed measured by the test of 10 m
Time Frame
6 months in each crossover period
Title
Measures of motor function according a Motor Function Measure scale (MFM )
Time Frame
6 months in each crossover period
Title
Muscular endurance is measured by the test of 2 minutes walk
Time Frame
6 months in each crossover period
Title
Measurement of the maximum voluntary contraction of the quadriceps
Time Frame
6 months in each crossover period
Title
The measurement of the endurance of the quadriceps
Time Frame
6 months in each crossover period
Title
Assessment of dyspnea according Borg scale
Time Frame
6 months in each crossover period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
For healthy volunteers:
volunteers >18 and <60 years old
Informed written consent
Health insurance
Exclusion Criteria:
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
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brigitte ESTOURNET, MD, PhD
Organizational Affiliation
Neuro-Respiratory Rehabilitation Service, Raymond Poincaré Hospital, 92380 Garches, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
UMR8251 University Paris Diderot / CNRS
City
Paris
ZIP/Postal Code
75013
Country
France
12. IPD Sharing Statement
Learn more about this trial
Pharmacological Treatment of a Rare Genetic Disease: N-acetylcysteine in Myopathy Associated Selenoprotein N-related Myopathy (SEPN1-RM)
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