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

NCT ID: NCT02505087

Last Updated: 2020-09-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2020-08-31

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.

Conditions

Selenoprotein N-related Myopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo followed by N-Acetylcysteine

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

Group Type: ACTIVE_COMPARATOR

Placebo followed by N-Acetylcysteine

Intervention Type: DRUG

Arm receiving placebo for 6 months then N-acetylcysteine (NAC) for 6 months. Treatment periods are separated by a 2 month washout.

N-Acetylcysteine followed by Placebo

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

Group Type: EXPERIMENTAL

N-Acetylcysteine followed by Placebo

Intervention Type: DRUG

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

Treatment periods are separated by a 2 month washout.

Healthy volunteers

The purpose of this group is to collect reference values for biochemical markers.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brigitte ESTOURNET, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Neuro-Respiratory Rehabilitation Service, Raymond Poincaré Hospital, 92380 Garches, France

Locations

UMR8251 University Paris Diderot / CNRS

Paris, , France

Countries

France

Other Identifiers

P100152

Identifier Type: -

Identifier Source: org_study_id