NF-κB Inhibition in Amyotrophic Lateral Sclerosis

Phase 2

• Conditions: ALS
• Interventions: Drug: Placebo; Drug: Withania somnifera

• Registration Number: NCT05031351
• Lead Sponsor: Sunnybrook Health Sciences Centre

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.

Study Timeline

• Study First Submitted: 2021-08-05
• Study First Submitted QC: 2021-08-26
• Study First Posted: 2021-09-01
• Study Start: 2021-10-19
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-01
• Last Update Posted: 2022-06-06
• Primary Completion: 2022-07
• Study Completion: 2022-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 75

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matched capsules twice a day
High dosage Withania somnifera	Withania somnifera	544mg oral twice a day
Medium dosage Withania somnifera	Withania somnifera	272mg oral twice a day

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events (safety)	From Baseline visit until end of study visit (Week 9)	Incidence of adverse events

Secondary Outcome Measures

Name	Time	Method
Change in RMT values	Baseline to 8 weeks	Resting motor threshold (RMT) measured by transcranial magnetic stimulation (TMS).
Change in strength duration time constant	Baseline to 8 weeks	This is a lower motor neuron excitability parameter measured by threshold tracking nerve excitability testing (NET).
Change in recovery cycle	Baseline to 8 weeks	This is a lower motor neuron excitability parameter measured by threshold tracking nerve excitability testing (NET).
Change in SICI values	Baseline to 8 weeks	Short-interval intracortical inhibition (SICI) measured by transcranial magnetic stimulation (TMS).

Trial Locations

Locations (1)

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada