Selenoprotein N-related MyopathyPhase 2/3SelNacNCT02505087
Pharmacological Treatment of a Rare Genetic Disease: N-acetylcysteine in Myopathy Associated Selenoprotein N-related Myopathy (SEPN1-RM)
A Phase 2/3 study of Selenoprotein N-related Myopathy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Selenoprotein N-related Myopathy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2015to 31 Aug 2020
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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
- Being tested
- N-Acetylcysteine followed by Placebo, Placebo followed by N-Acetylcysteine
- Keywords
- Selenoprotein N-related myopathy, biomarkers, washout, N-ACETYLCYSTEINE
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-Acetylcysteine followed by PlaceboDrug
Arm receiving N-Acetylcysteine (NAC) for 6 months and then placebo for 6 months.
Treatment periods are separated by a 2 month washout.
Placebo followed by N-AcetylcysteineDrug
Arm receiving placebo for 6 months then N-acetylcysteine (NAC) for 6 months. Treatment periods are separated by a 2 month washout.
| Study group | Role | What they receive |
|---|---|---|
| Placebo followed by N-Acetylcysteine | Active comparator | Arm receiving placebo for 6 months, then N-Acetylcysteine (NAC) for 6 months. Receives: Drug: Placebo followed by N-Acetylcysteine |
| N-Acetylcysteine followed by Placebo | Experimental | Arm receiving N-Acetylcysteine (NAC) for 6 months and then placebo for 6 months. Receives: Drug: N-Acetylcysteine followed by Placebo |
| Healthy volunteers | No intervention | The purpose of this group is to collect reference values for biochemical markers. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of reduced glutathione and oxidized glutathione in blood erythrocytes.
Measured: 6 months in each period
Secondary outcomes (10)
measure of health status according The 36-Item Short Form Health Survey (SF36)
Measured: 6 months in each crossover period
Evaluate the impact of fatigue according the Fatigue Severity Scale (FSS)
Measured: 6 months in each crossover period
Measurement of biomarkers in blood samples, muscle and fibroblasts
Measured: 6 months in each crossover period
Measure of Activity Limitation (Activlim test)
Measured: 6 months in each crossover period
Running speed measured by the test of 10 m
Measured: 6 months in each crossover period
Measures of motor function according a Motor Function Measure scale (MFM )
Measured: 6 months in each crossover period
Muscular endurance is measured by the test of 2 minutes walk
Measured: 6 months in each crossover period
Measurement of the maximum voluntary contraction of the quadriceps
Measured: 6 months in each crossover period
The measurement of the endurance of the quadriceps
Measured: 6 months in each crossover period
Assessment of dyspnea according Borg scale
Measured: 6 months in each crossover period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2015 (estimated)
- Study startSep 2015
- Primary completion24 Apr 2018
- Study completion31 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Selenoprotein N-related MyopathyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brigitte ESTOURNET, MD, PhD, Principal investigator, Neuro-Respiratory Rehabilitation Service, Raymond Poincaré Hospital, 92380 Garches, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02505087
- Sponsor's protocol ID
- P100152
- Acronym
- SelNac
- Status last verified
- Nov 2017
- First submitted
- 25 Jun 2015
- Last updated
- 29 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02505087
- Acronym / sponsor ID
- SelNac / P100152
- Conditions
- Selenoprotein N-related Myopathy
- Keywords
- Selenoprotein N-related myopathy, biomarkers, washout, N-ACETYLCYSTEINE
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Sep 2015 (actual)
- Primary completion
- 24 Apr 2018 (actual)
- Study completion
- 31 Aug 2020 (actual)
- First posted
- 22 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo followed by N-Acetylcysteine | Active comparator | Drug: Placebo followed by N-AcetylcysteineArm receiving placebo for 6 months, then N-Acetylcysteine (NAC) for 6 months. |
| N-Acetylcysteine followed by Placebo | Experimental | Drug: N-Acetylcysteine followed by PlaceboArm receiving N-Acetylcysteine (NAC) for 6 months and then placebo for 6 months. |
| Healthy volunteers | No intervention | –The purpose of this group is to collect reference values for biochemical markers. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- For patients:
- For healthy volunteers:
Key exclusion criteria (17 listed)
- For patients:
- For healthy volunteers:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-Acetylcysteine followed by PlaceboArm receiving N-Acetylcysteine (NAC) for 6 months and then placebo for 6 months. Treatment periods are separated by a 2 month washout. | Drug | N-Acetylcysteine followed by Placebo |
| Placebo followed by N-AcetylcysteineArm receiving placebo for 6 months then N-acetylcysteine (NAC) for 6 months. Treatment periods are separated by a 2 month washout. | Drug | Placebo followed by N-Acetylcysteine |
Primary outcome
Ratio of reduced glutathione and oxidized glutathione in blood erythrocytes.
Time frame: 6 months in each period
10 secondary outcomes
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
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brigitte ESTOURNET, MD, PhD principal investigator
Neuro-Respiratory Rehabilitation Service, Raymond Poincaré Hospital, 92380 Garches, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study of Selenoprotein N-related Myopathy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ratio of reduced glutathione and oxidized glutathione in blood erythrocytes. (time frame: 6 months in each period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2020.