NF-κB Inhibition in Amyotrophic Lateral Sclerosis

ALS Clinical Trial

— NIALS  

Official title:

Nuclear Factor Kappa Beta Inhibition in Patients With Amyotrophic Lateral Sclerosis: A Phase II Randomized Placebo Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05031351
• Other study ID #: 032-2017
• Status: Recruiting
• Phase: Phase 2
• Start date: October 19, 2021
• Est. completion date: September 2022

Study information

• Verified date: June 2022
• Source: Sunnybrook Health Sciences Centre
• Contact: Jake Wimmer
• Phone: 416-480-6100
• Email: jake.wimmer[@]sri.utoronto.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: September 2022
• Est. primary completion date: July 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• ALS
• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Withania somnifera
Nuclear Factor Kappa Beta Inhibitor
• Placebo
Placebo Comparator

Locations

Country	Name	City	State
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incident cases of ALSFRS-R score changes of 4 or more points	Any incident case of = 4-point increase in the ALS Functional Rating Scale-Revised (ALSFRS-R) scores or significant clinical improvement at week 8 will be reported. Changes in pro-inflammatory tests (CRP and IL-6) from baseline to Week 8 will be assessed.	Baseline to 9 weeks
Other	Change in serum IL-6 levels	Serum IL-6 levels will serve as an indirect marker of NF-kB inhibition and target engagement.	Baseline to 8 weeks
Primary	Incidence of adverse events (safety)	Incidence of adverse events	From Baseline visit until end of study visit (Week 9)
Secondary	Change in SICI values	Short-interval intracortical inhibition (SICI) measured by transcranial magnetic stimulation (TMS).	Baseline to 8 weeks
Secondary	Change in RMT values	Resting motor threshold (RMT) measured by transcranial magnetic stimulation (TMS).	Baseline to 8 weeks
Secondary	Change in recovery cycle	This is a lower motor neuron excitability parameter measured by threshold tracking nerve excitability testing (NET).	Baseline to 8 weeks
Secondary	Change in strength duration time constant	This is a lower motor neuron excitability parameter measured by threshold tracking nerve excitability testing (NET).	Baseline to 8 weeks