NF-κB Inhibition in Amyotrophic Lateral Sclerosis

NCT05031351 | Unknown Phase 2 DMC

• 1 other identifier: 032-2017
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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).

Conditions

ALS

Keywords

Withania somnifera; Ashwagandha; Nuclear Factor Kappa Beta Inhibition; Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events (safety)

  Incidence of adverse events

  From Baseline visit until end of study visit (Week 9)

Secondary Outcomes (4)

• Change in SICI values

  Baseline to 8 weeks

• Change in RMT values

  Baseline to 8 weeks

• Change in recovery cycle

  Baseline to 8 weeks

• Change in strength duration time constant

  Baseline to 8 weeks

Other Outcomes (2)

• Incident cases of ALSFRS-R score changes of 4 or more points

  Baseline to 9 weeks

• Change in serum IL-6 levels

  Baseline to 8 weeks

Study Arms (3)

High dosage Withania somnifera

EXPERIMENTAL

544mg oral twice a day

Drug: Withania somnifera

Medium dosage Withania somnifera

EXPERIMENTAL

272mg oral twice a day

Drug: Withania somnifera

Placebo

PLACEBO COMPARATOR

Matched capsules twice a day

Drug: Placebo

Interventions

Withania somnifera DRUG

Nuclear Factor Kappa Beta Inhibitor

High dosage Withania somnifera; Medium dosage Withania somnifera

Placebo DRUG

Placebo Comparator

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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:
• Substance abuse within the past year
• Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active malignancy or infectious disease
• Acquired Immunodeficiency Syndrome (AIDS) or AIDS-related complex
• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Ashwagandha

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

Study Officials

• Agessandro Abrahao, MD, MSc

  Sunnybrook Research Institute, University of Toronto

  PRINCIPAL INVESTIGATOR

• Lorne Zinman, MD, MSc

  Sunnybrook Research Institute, University of Toronto

  STUDY DIRECTOR

Central Study Contacts

Jake Wimmer

CONTACT

416-480-6100; jake.wimmer@sri.utoronto.ca

Shirley Pham

CONTACT

+1 (416)480-6860; shirley.pham@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2021
• First Posted: September 1, 2021
• Study Start: October 19, 2021
• Primary Completion: July 1, 2022
• Study Completion: September 1, 2022
• Last Updated: June 6, 2022

Record last verified: 2022-06

Locations

CA (1)