Antioxidant Therapy in RYR1-Related Congenital Myopathy

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02362425
• Date of registration: 12/02/2015
• Prospective Registration: Yes
• Primary sponsor: National Institute of Nursing Research (NINR)
• Public title: Antioxidant Therapy in RYR1-Related Congenital Myopathy RYR1
• Scientific title: Antioxidant Therapy in RYR1-Related Congenital Myopathy
• Date of first enrolment: February 12, 2015
• Target sample size: 63
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02362425
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Suzanne J Wingate, C.R.N.P.
• Affiliation: National Institute of Nursing Research (NINR)

Key inclusion & exclusion criteria

- EXCLUSION CRITERIA - PATIENTS:

- Adults who cannot provide their own consent and pediatric participants who do not have
a parent able to provide consent.

- Patients with a history of liver disease (Liver Function Tests will be collected at
baseline and

at each study visit as a precautionary measure). Liver disease is defined as moderate to
severe hepatic impairment based on the following:

- Alanine Aminotransferase (ALT) greater than or equal to 8x upper limit of normal (ULN)
with total bilirubin 2x ULN (plus >35% direct bilirubin) and/or International
normalized ratio (INR) >1.5 or

- Gamma-glutamyl transferase (GGT) > 2-3x ULN with bilirubin 2x ULN (plus >35% direct
bilirubin) and/or INR

- Patients with a history of peptic ulcers, gag reflex depression, and esophageal
varices. Patients with gastrostomy tubes may be considered for participation, in
the case of gag reflex depression or other swallowing or feeding difficulties.

- Patients who have a severe pulmonary dysfunction (FEV1< 40% predicted) or
evidence of pulmonary exacerbation. Pulmonary exacerbations refer to an acute
worsening of respiratory symptoms that result from a decline in lung function.
Participants may present with increased coughing, increased dyspnea, increased
haemoptysis, increased fatigue, decreased pulmonary function by a min of 10%, or
a change in sputum color.

- Pregnant and breastfeeding women.

- Consumption of antioxidants [including NAC, GSH, melatonin, Immunocal (Immunotac

Research, Vandreuil-Dorion, QC, Canada), Nacystelyn (Galephar, Brussels)] in the 4 weeks
before recruitment.

-Daily use of acetaminophen (including Percocet, Vicodin, Oxycodone, Excedrin, and other

acetaminophen-containing drugs), nitroglycerine, or carbamazepine during the past 7 days.

- Current use of Angiotensin-converting enzyme (ACE) inhibitors or Angiotensin Receptor
Blockers (ARBs).

- Patients who have ever used Beta2-adrenergic agonist tablets, for the purpose of
increasing muscle mass (such as albuterol tablets).

- For the muscle biopsy procedure only (second and third visits, if applicable):
Patients who have taken Aspirin, Ibuprofen, Advil, Motrin, or Aleve within the 3 days
prior to the muscle biopsy procedure, and/or patients who have taken Plavix, fresh
garlic, gingko, or ginseng 5 days prior to the muscle biopsy.

- Participation in trials for other therapeutic investigational drugs simultaneously or
4 weeks before recruitment.

- Other clinically significant medical disease that, in the judgment of the
investigators, would expose the patient to undue risk of harm or prevent the patient
from completing the study. Examples include anemia (defined as Hgb < 8 gm/dl), an
inability to walk safely without assistance for at least 6 minutes, and/or an
inability to consume at least 6 ounces of fluid, 3 times a day, either orally or via
G-tube. Patients with comorbidities (i.e. cancer, epilepsy) will be carefully assessed
to determine if their comorbidity could lead to confounding or safety issues, should
their participation continue.

EXCLUSION CRITERIA - HEALTHY VOLUNTEERS:

- Diagnosis of RYR1-related myopathy or other neurological disorder (by neurological
exam, genetic testing, or muscle biopsy

- Complaints of fatigue or weakness

- Consumption of antioxidants [including NAC, GSH, melatonin, Immunocal (Immunotac

- Research, Vandreuil-Dorion, QC, Canada), Nacystelyn (Galephar, Brussels)] in the 4
weeks before recruitment.

- Use of Beta2-adrenergic agonists.



Age minimum: 7 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Neuromuscular Disease

Intervention(s)

Drug: N-acetylcysteine

Drug: Placebo

Primary Outcome(s)

Six Minute Walk Test (6MWT) [Time Frame: 12 months]

Urine 15-F2t Isoprostane Concentration [Time Frame: 12 months]

Secondary Outcome(s)

Hand Pinch Strength [Time Frame: 12 months]

Motor Function Measure-32 (MFM-32) Domain 1 (D1) [Time Frame: 12 months]

Multidimensional Fatigue Inventory-20 (MFI-20) Mental Fatigue Score [Time Frame: 12 months]

Pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue [Time Frame: 12 months]

Hand Grip Strength [Time Frame: 12 months]

Motor Function Measure-32 (MFM-32) Domain 2 (D2) [Time Frame: 12 months]

Multidimensional Fatigue Inventory-20 (MFI-20) Reduced Activity Score [Time Frame: 12 months]

Pediatric Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score [Time Frame: 12 months]

Adult Quality of Life in Neurological Disorders (NeuroQoL) Fatigue [Time Frame: 12 months]

Blood Glutathione Reduced (GSH):Oxidized (GSSG) Ratio [Time Frame: Baseline]

DCF-fluorescence Intensity (AU) [Time Frame: 12 months]

Descend Steps [Time Frame: 12 months]

Motor Function Measure-32 (MFM-32) Domain 3 (D3) [Time Frame: 12 months]

Peak Torque Extension [Time Frame: 12 months]

Multidimensional Fatigue Inventory-20 (MFI-20) Reduced Motivation Score [Time Frame: 12 months]

Peak Torque Flexion [Time Frame: 12 months]

Time to Ascend Steps (Seconds) [Time Frame: 12 months]

Supine to Stand [Time Frame: 12 months]

Walk/Run 10 Meters [Time Frame: 12 months]

Adult Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue [Time Frame: 12 months]

Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score [Time Frame: 12 months]

Pediatric Quality of Life in Neurological Disorders (NeuroQoL) Fatigue [Time Frame: 12 months]

Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Trial Outcome Index [Time Frame: 12 months]

Multidimensional Fatigue Inventory - 20 (MFI-20) General Fatigue Score [Time Frame: 12 months]

Motor Function Measure-32 (MFM-32) Total Score [Time Frame: 12 months]

Multidimensional Fatigue Inventory-20 (MFI-20) Physical Fatigue Score [Time Frame: 12 months]

Secondary ID(s)

15-NR-0072

150072

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 24/12/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02362425