Amyotrophic Lateral Sclerosis
Conditions
Keywords
Amyotrophic Lateral Sclerosis, Acetylcysteine, EH301, ALSFRS-R, ALS, NAC, Hospital Universitario Donostia, Biogipuzkoa, Adolfo López de Munain, NADALS-001-ALS-2021, Open Label Extension, NADALS
Brief summary
This study is designed to evaluate whether a combination of N-acetylcysteine (NAC) and EH-301 can slow down or improve symptoms of amyotrophic lateral sclerosis (ALS). Researchers will assess changes in disease progression using the ALS Functional Rating Scale-Revised (ALSFRS-R), a standard tool for measuring daily functioning in people with ALS. The main question is whether taking NAC together with EH-301 can prevent symptom worsening and possibly improve existing ALS symptoms. Participants will be randomly assigned to receive either the active combination (NAC + EH-301) or matching placebos for 6 months. During this period, they will attend regular clinic visits for evaluations, tests, and safety monitoring. After completing the initial 6-month phase, all participants may choose to join a 6-month open-label extension, where everyone receives the active treatment regardless of their original group.
Interventions
DRUGAcetylcysteine
Daily dose of 600mg of effervescent powder
DIETARY_SUPPLEMENTEH301
Daily dose of 1800mg of capsules
DRUGRiluzole
Daily dose of 100mg of tablets
Sponsors
Biogipuzkoa Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Pharmacy team
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients diagnosed with ALS according to the Gold Coast criteria; 2. Disease duration ≤ 18 months; 3. Men and women aged 18 to 75 years; 4. Total ALSFRS-R score ≥ 30 for all 12 categories; 5. Forced vital capacity (FVC) ≥70%; 6. The participant must receive treatment with Riluzole (50 mg twice daily) for ≥30 days prior to Day 1 (Visit 2) and is expected to remain on that dose until the final study visit. 7. Willingness and ability of the patient to comply with the requirements of the protocol during the study; 8. Sign written informed consent prior to any study-related procedure; 9. Acceptance by women to use at least one highly effective method of contraception during the study 30 days prior to taking the nutraceutical and investigational drug and throughout the study. The following are considered highly effective contraceptive methods: * Combined hormonal methods (oral, patches, injectables, or implants). * Hormonal or copper intrauterine devices (IUDs). * Previous surgical sterilization (bilateral tubal ligation). * Total sexual abstinence when consistent with the patient's usual lifestyle. 10. Acceptance by men included in the study of the use of condoms in combination with an effective contraceptive method used by their female partner of childbearing age during treatment.
Exclusion criteria
1. Presence of other neurodegenerative diseases; 2. Significant cognitive impairment and/or dementia; 3. Any psychiatric illness that could interfere with the study; 4. Use of dietary supplements with high doses of vitamin B3 in the 30 days prior to inclusion in the study; 5. Severe heart disease; 6. Moderate to severe lung disease, such as emphysema, stage III-IV COPD; 7. Uncontrolled chronic asthma; 8. Active cancer; 9. Any metabolic, neoplastic, physically or mentally debilitating disease that could put the subject at risk or interfere with the study results; 10. Genetically confirmed mitochondrial disease; 11. Tracheostomized and/or gastrostomized patients; 12. Participation in any clinical trial with an investigational product within 30 days or five half-lives of the previous agent, whichever is longer, prior to dosing; 13. Any clinically significant laboratory abnormality that could directly affect compliance or safety; 14. Allergy to NAC or any excipient, either in the investigational drug or in the EH301 nutraceutical; 15. Patients with a short life expectancy in the investigator's judgment. 16. \[Women only\] Pregnancy or breastfeeding for women of childbearing potential (i.e., \<2 years postmenopausal or not surgically sterile); 17. The participant is unwilling to use highly effective contraception during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ALSFRS-R scale | Up to 48 weeks | Change from baseline in the ALS Functional Rating Scale-Revised (ALSFRS-R) \[range from 0 to 48, being 48 normal function and 0 complete function loss\] to assess disease progression and evaluate the clinical efficacy and safety of the combination of NAC and EH301 during the randomized treatment period (24 weeks) and, for participants who enter the open-label extension, up to 48 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle strength | Up to 48 weeks | Muscle strength measured by hand dynamometry during the randomized treatment period (24 weeks) and, for participants who enter the open-label extension, up to 48 weeks. |
| Ventilation-free survival | Up to 48 weeks | Percentage of participants who remain alive without requiring tracheotomy or permanent invasive ventilation during the randomized period (24 weeks) or, for those who enter the open-label extension, up to 48 weeks. |
| Quality of life (ALSAQ-40) | Up to 48 weeks | Quality of life assessed using the ALSAQ-40 questionnaire \[range from 0 to 100, being 0 best health status and 100 worst health status\] during the randomized treatment period (24 weeks) and, for participants who enter the open-label extension, up to 48 weeks. |
| Respiratory function (%FVC) | Up to 48 weeks | Respiratory function measured as percent predicted forced vital capacity (%FVC) during the randomized treatment period (24 weeks) and, for participants who enter the open-label extension, up to 48 weeks. |
| Time to gastrostomy | Up to 48 weeks | Time from baseline to placement of gastrostomy tube (percutaneous endoscopic gastrostomy or radiologically inserted gastrostomy). Participants in the open-label extension are followed for events up to 48 weeks. |
| Combined Assessment of Function and Survival (CAFS) | Up to 48 weeks | Combined Assessment of Function and Survival (CAFS) score calculated using ALSFRS-R change and survival status \[no fixed numerical range; ranking score where higher values indicate better combined functional status and survival\] during the randomized treatment period (24 weeks) and, for participants who enter the open-label extension, up to 48 weeks. |
| Neurofilament light chain (NfL) biomarker | Up to 48 weeks | Neurofilament light chain (NfL) levels in serum and cerebrospinal fluid will be measured for biomarker assessment. Analyses will evaluate the change from baseline in NfL concentrations during the randomized treatment period (24 weeks) and, for participants who enter the open-label extension, up to 48 weeks. |
| Serum lipidomic profile | Up to 48 weeks | Serum lipidomic components will be measured for biomarker assessment. Analyses will evaluate the change from baseline in the serum lipidomic profile during the randomized treatment period (24 weeks) and, for participants who enter the open-label extension, up to 48 weeks. |
Countries
Spain
Contacts
CONTACTLara Alameda Calvo
Outcome results
None listed