NF-κB Inhibition in Amyotrophic Lateral Sclerosis

NCT ID: NCT05031351

Last Updated: 2022-06-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-19
• Study Completion Date: 2022-09-30

Brief Summary

This is a Phase II, single centre, randomized, parallel, double blind, placebo-controlled clinical trial to determine the safety of Withania somnifera in participants with Amyotrophic Lateral Sclerosis (ALS).

Detailed Description

There will be up to 75 participants randomized 1:1:1 to receive either high dosage Withania somnifera extract (1088 mg daily), medium dosage Withania somnifera extract (544 mg daily) or matching placebo. The study will consist of a Screening Period, Randomization visit, Baseline visit, and Follow-up visits. The treatment period will be 8 weeks and a final follow up call will occur at Week 9.

Conditions

ALS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

High dosage Withania somnifera

544mg oral twice a day

Group Type: EXPERIMENTAL

Withania somnifera

Intervention Type: DRUG

Nuclear Factor Kappa Beta Inhibitor

Medium dosage Withania somnifera

272mg oral twice a day

Group Type: EXPERIMENTAL

Withania somnifera

Intervention Type: DRUG

Nuclear Factor Kappa Beta Inhibitor

Placebo

Matched capsules twice a day

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo Comparator

Interventions

Withania somnifera

Nuclear Factor Kappa Beta Inhibitor

Intervention Type: DRUG

Placebo

Placebo Comparator

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosed with laboratory supported probable, clinically possible, probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria (83) (Appendix A)
• Disease duration from symptom onset no greater than 36 months at the Screening Visit
• Aged 18 years or older
• Capable of providing informed consent and complying with study procedures
• If taking riluzole, on a stable dose for at least 30 days prior to Screening Visit
• If taking edaravone, on a stable dose for at least one cycle prior to Screening Visit
• If on BiPAP, average usage of no more than 12 hours per day at time of Screening Visit
• Able to swallow a capsule at Baseline Visit
• Fluency in English or French

Exclusion Criteria

• Exposure to any investigational agent or Withania somnifera (Ashwagandha) within 30 days prior to the Screening Visit; simultaneous participation in other observational studies is allowed upon Site Investigator approval
• Presence of any of the following clinical conditions:

1. Substance abuse within the past year

2. Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active malignancy or infectious disease

3. Acquired Immunodeficiency Syndrome (AIDS) or AIDS-related complex

4. Unstable psychiatric illness defined as psychosis (hallucinations or delusions) or untreated major depression within 90 days prior to the Screening Visit

• Hypersensitivity or allergy to Withania somnifera
• Uncontrolled diabetes with severe associated complications (such as neuropathy)
• Untreated hypertension, active stomach ulcers, or untreated thyroid disorder
• Previously diagnosed auto-immune condition with or without neurological manifestations (e.g. multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis, etc.)
• Current or planned use of oral, intramuscular or intravenous steroid drugs (such as prednisone, prednisolone, dexamethasone, triamcinolone, methylprednisolone, oxandrolone, and others) or immunosuppressant drugs (azathioprine, mycophenolate, tacrolimus, sirolimus, cyclophosphamide, and others) for more than 7 days
• Planned consumption of alcohol, other drugs or natural health products with sedative and anxiolytics properties while taking study drugs (8 week duration)
• Current or planned use of continuous subcutaneous, intravenous or oral anticoagulant drugs
• Scheduled for surgery under general anesthetic within 14 days of Screening Visit
• Pregnancy or planned pregnancy. Women of childbearing potential must have a negative pregnancy test and be non-lactating at the Screening Visit
• Insertion of a diaphragm pacing system

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Agessandro Abrahao, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Research Institute, University of Toronto

Lorne Zinman, MD, MSc

Role: STUDY_DIRECTOR

Sunnybrook Research Institute, University of Toronto

Locations

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Jake Wimmer

Role: CONTACT

jake.wimmer@sri.utoronto.ca

416-480-6100 ext. 87561

Shirley Pham

Role: CONTACT

shirley.pham@sunnybrook.ca

+1 (416)480-6860

Facility Contacts

Lorne Zinman

Role: primary

Lorne.Zinman@sunnybrook.ca

Agessandro Abrahao

Role: backup

agessandro.abrahao@sunnybrook.ca

Other Identifiers

032-2017

Identifier Type: -

Identifier Source: org_study_id