Evaluation of the Combined Therapy of EH-301 and N-acetylcysteine Together With Riluzole in Amyotrophic Lateral Sclerosis (ALS)

NCT07414212 | Recruiting Phase 1

• 2 other identifiers: NADALS-001-ALS-20212024-519857-13-00
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Amyotrophic Lateral Sclerosis

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

Outcome Measures

Primary Outcomes (1)

• ALSFRS-R scale

  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.

  Up to 48 weeks

Secondary Outcomes (8)

• Muscle strength

  Up to 48 weeks

• Ventilation-free survival

  Up to 48 weeks

• Quality of life (ALSAQ-40)

  Up to 48 weeks

• Respiratory function (%FVC)

  Up to 48 weeks

• Time to gastrostomy

  Up to 48 weeks

Study Arms (2)

Acetylcysteine + EH301

EXPERIMENTAL

Combination of 600 mg of NAC + 1800 mg of EH301 (1500 mg of NR + 300 mg of PTER) + 100 mg of Riluzole (standard treatment for both arms)

Drug: Acetylcysteine; Dietary Supplement: EH301; Drug: Riluzole

Acetylcysteine Placebo + EH301 Placebo

PLACEBO COMPARATOR

Combination of NAC placebo + EH301 placebo + 100 mg of Riluzole (standard treatment for both arms)

Drug: Riluzole

Interventions

Acetylcysteine DRUG

Daily dose of 600mg of effervescent powder

Also known as: NAC

Acetylcysteine + EH301

EH301 DIETARY_SUPPLEMENT

Daily dose of 1800mg of capsules

Also known as: Nicotinamide riboside and pterostilbene

Acetylcysteine + EH301

Riluzole DRUG

Daily dose of 100mg of tablets

Acetylcysteine + EH301; Acetylcysteine Placebo + EH301 Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with ALS according to the Gold Coast criteria;
• Disease duration ≤ 18 months;
• Men and women aged 18 to 75 years;
• Total ALSFRS-R score ≥ 30 for all 12 categories;
• Forced vital capacity (FVC) ≥70%;
• 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.
• Willingness and ability of the patient to comply with the requirements of the protocol during the study;
• Sign written informed consent prior to any study-related procedure;
• 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.
• 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.

You may not qualify if:

• Presence of other neurodegenerative diseases;
• Significant cognitive impairment and/or dementia;
• Any psychiatric illness that could interfere with the study;
• Severe heart disease;
• Moderate to severe lung disease, such as emphysema, stage III-IV COPD;
• Uncontrolled chronic asthma;
• Active cancer;
• Any metabolic, neoplastic, physically or mentally debilitating disease that could put the subject at risk or interfere with the study results;
• Genetically confirmed mitochondrial disease;
• Tracheostomized and/or gastrostomized patients;
• 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;
• Any clinically significant laboratory abnormality that could directly affect compliance or safety;
• Allergy to NAC or any excipient, either in the investigational drug or in the EH301 nutraceutical;
• Patients with a short life expectancy in the investigator's judgment.
• \[Women only\] Pregnancy or breastfeeding for women of childbearing potential (i.e., \<2 years postmenopausal or not surgically sterile);

Sponsors & Collaborators

• Biogipuzkoa Health Research Institute: lead

Study Sites (1)

Hospital Universitario Donostia

San Sebastián, Guipuzcoa, 20003, Spain

RECRUITING

Related Links

• CTIS

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Acetylcysteine; nicotinamide-beta-riboside; Pterocarpus marsupium; Riluzole

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Thiazoles; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Lara Alameda Calvo

CONTACT

+34 943006140; lara.alamedacalvo@bio-gipuzkoa.eus

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Pharmacy team
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2026
• First Posted: February 17, 2026
• Study Start: November 25, 2025
• Primary Completion (Estimated): November 25, 2026
• Study Completion (Estimated): November 25, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)