Therapeutic Antioxidant Supplementation (TAS-SS21)

Therapeutic Antioxidant Supplementation for Enhancement of Neural Protection From Free-iron Toxicity in Superficial Siderosis

A remotely administered study, non-randomized, non-blinded, controlled parallel assignment phase 2 trial to determine if oral inosine or inositol hexaphosphate will provide an effective long-term therapy to combat or slow neural damage progression either concurrently with existing iron chelation therapy or during the natural course of the disorder. Clinical changes in hearing, balance, and mobility, and cognition will be assessed for 36 months through patient-reported outcomes of study assigned assessments.

Study Overview

• Status: Not yet recruiting
• Conditions: Superficial Siderosis
• Intervention / Treatment: Dietary supplement: Inosine; Dietary supplement: IP6

Detailed Description

Capsules containing over-the-counter dietary supplement formulas of inosine 500 mg or 500 mg of inositol hexaphosphate(IP6) will be taken orally, two capsules two times per day for 36 months. Initial screening will determine patient arm assignment.

Before dosing begins, patients will submit copies of previous audiogram results (3yrs), radiology reports (3yrs), and MRI series (3yrs) if available and complete baseline assessment activities: Montreal Cognitive Assessment (MoCA) administered remotely, Timed Up, and Go (TUG), 2-Minute Walk Test (2-MWT), The Activities-specific Balance Confidence (ABC) Scale, iSS-QoL (custom) patient outcome reported

Assessment will take place four times: baseline, end-of-year 1 (12mo), end-of-year 2 (24mo), end-of-study (36mo).

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rori-Suzanne Daniel; Phone Number: 9035594123; Email: administrator@superficialsiderosis.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 77 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Confirmed diagnosis of iSS (superficial siderosis of the CNS)

No illegal drug use

No history of myocardial infarction or stroke

No history of severe chronic obstructive pulmonary disease

Can safely swallow large capsules

Exhibits at least one confirmed iSS related symptom: Hearing Loss, Balance, Memory/Cognitive problems

Does not have a known hypersensitivity or intolerance to any study antioxidant

Has not taken part in another treatment study for any condition within the last 30 days (about four and a half weeks)

Not currently pregnant or breastfeeding

Exclusion Criteria:

Inosine Arm Exclusion :

Diagnosed with urate urolithiasis, or recurrent urolithiasis, all unknown type

History of Gout

History of Kidney Stones

P6 Arm Exclusion

Long-term anticoagulant

Known or suspected active bleed into the CNS

Currently undergoing deferiprone chelation therapy

Plan to begin deferiprone chelation therapy within three years

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Over-the-Counter Dietary Supplement Inosine; capsules containing 500 mg of inosine Two capsules Twice Daily Other Name: hypoxanthine 9-β-D-ribofuranoside 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-hydroxymethyl) oxolan-2-yl]-1H-purin-6-one	Dietary supplement: Inosine; Patients will be dosed with two 500 mg capsules of Inosine twice daily for 36 months
Experimental: Over-the-Counter Dietary Supplement IP6; capsules containing 500mg of IP6 Two capsules Twice Daily Other Name: Inositol hexaphosphate (1R,2S,3r,4R,5S,6s)-cyclohexane-1,2,3,4,5,6-hexayl hexakis[dihydrogen (phosphate)]	Dietary supplement: IP6; Patients will be dosed with two 500 mg capsules of IP6 twice daily for 36 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Slow the Rate of Clinical Decline	Deceleration of clinical decline will be quantified by evaluating three primary areas- hearing, balance and mobility, and cognition. End-of-study quantifiable slowing of the historical and year-1 mean rate of decline across all three study areas with a measurable increase on Year-3 iSS-QOL from Year-1 iSS-QOL scoring.	36 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Efficacy: Rate of Adverse Event Development [Safety and Tolerability}	Therapeutic use of antioxidants through a safe, effective dose range and schedule to the extent that the risk-benefit relationship is acceptable for the patient. Evaluation will include the overall adverse event (AE) and serious AE (SAE) rate.	36 Months
Clinical Efficacy: Improved Quality of Life	The rate of change in points on the iSS-QoL(custom) from baseline assessment to end-of-study will be scored based on 16 questions with a point range of 1-5. Higher end-of-study scores indicate greater satisfaction.	36 Months
Clinical Efficacy: Rate of Change in Montreal Cognitive Assessment (MoCA)	The rate of change in points on the Montreal Cognitive Assessment (MoCA) scale from baseline assessment to end-of-study will be assessed for patients in each treatment group. The MoCA assesses attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Points (range 0-30) are awarded for the correct completion of MoCA tasks. Cognition decline will be defined as ≥ 3pt decline of total MoCA score from baseline assessment to final 36mo testing assessment.	36 Months
Clinical Efficacy: Rate of Change in Hearing	The baseline audiogram will be compared to the post-study audiogram for each patient. The hearing levels in decibels against the frequency in hertz will be compared pre-study, baseline, and end-of-study for average rate-of-decline. A paired t-test will be used to determine statistical significance in the average difference in the threshold hearing level at any particular frequency.	36 Months
Clinical Efficacy: Rate of Change in Mobility and Balance	The Timed Up & Go (TUG), 2-Minute Walk Test (2MWT), and Activities-specific Balance Confidence (ABC) Scale will be scored individually. The baseline score will be compared to the annual and end-of-study scores for each patient. A paired t-test will be used to determine statistical significance in the average difference.	36 Months
Clinical Efficacy: Hemosiderin Reduction (IP6 Arm)	Visible hemosiderin deposition reduction on MRI series from baseline visit to end-of-study. MRIs will be objectively analyzed for changes in iron deposition.	36 Months

Collaborators and Investigators

• Sponsor: Superficial Siderosis Research Alliance Inc.
• Investigators: Study Director: Rori-Suzanne Daniel, Superfical Siderosis Research Alliance

Publications and helpful links

Helpful Links

• Superficial Siderosis Patient Registry
• Superficial Siderosis research Alliance

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): June 1, 2027
• Study Completion (Anticipated): September 1, 2027

Study Registration Dates

• First Submitted: May 12, 2021
• First Submitted That Met QC Criteria: May 12, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 4, 2022
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Neurodegenerative disorder; Hemosiderin; Iron Toxicity; Superficial siderosis of the CNS; Infratentorial superficial siderosis; Subpial
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Occupational Diseases; Pneumoconiosis; Lung Diseases, Interstitial; Lung Injury; Siderosis
• Other Study ID Numbers: SSRA0921

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No