Augmenting Cerebral Blood Flow to Treat Established Multiple Sclerosis

NCT02466074 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HSC-MS-14-0450
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate how improved cerebral blood flow affects the way in which newly formed MS lesions evolve and whether tissue repair is improved. Patients with multiple sclerosis (MS) will be treated with acetazolamide in daily divided doses and obtain MRI to determine how much and in which regions of the brain cerebral perfusion improves as well as the extent to which tissue integrity is improved in these areas.

Conditions

Multiple Sclerosis

Keywords

Acetazolamide; Lesions; Neurodegeneration; Repair

Outcome Measures

Primary Outcomes (1)

• Percent Change in Global Cerebral Blood Flow

  Percent change in global cerebral blood flow (CBF) after 24 weeks relative to pre-treatment baseline. Global CBF is determined using magnetic resonance imaging (MRI) methods. The data reported indicate the extent of change in global CBF--the higher the percent change, the greater the increase in global CBF and the better the outcome.

  baseline, 24 weeks

Secondary Outcomes (2)

• Percent Change in Tissue Integrity in White Matter (Mean Diffusivity)

  baseline, 24 weeks

• Percent Change in Tissue Integrity in White Matter (Fractional Anisotropy)

  baseline, 24 weeks

Other Outcomes (1)

• Composite Changes in Disability Measures

  1 year

Study Arms (2)

Acetazolamide

EXPERIMENTAL

Acetazolamide in oral daily divided dose administered for 6 consecutive months

Drug: Acetazolamide

Placebo

PLACEBO COMPARATOR

Placebo in oral daily divided dose administered for 6 consecutive months

Drug: Placebo

Interventions

Acetazolamide DRUG

see arm description

Also known as: Diamox

Acetazolamide

Placebo DRUG

Placebo arm

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of relapsing forms of multiple sclerosis using revised McDonald criteria
• Stable on any FDA-approved disease-modifying therapy. The term "stable" implies that the subject has not had change in therapy for any reason for the 6 months prior to study entry.
• Expanded Disability Status Scale (EDSS) score of 0-6.0 inclusive
• Understood and signed written informed consent, obtained prior to the study subject undergoing any study related procedure, including screening tests.

You may not qualify if:

• Known hypersensitivity to sulfonamides or derivatives
• Known history of renal or hepatic disease, cerebrovascular disease including stroke, transient ischemic attack, myocardial infarction, angina or congestive heart failure.
• Evidence to suggest hyponatremia or hypokalemia, marked kidney dysfunction defined as creatinine greater than 2.0 mg/dL or liver disease dysfunction defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than three-fold upper limit of normal (ULN).
• Evidence to suggest suprarenal gland failure.
• Evidence of hyperchloremic acidosis.
• Initiation of new immunosuppressant treatment after the subject becomes protocol-eligible (except for corticosteroids) or enrollment in a concurrent trial.
• Prior treatment with mitoxantrone, natalizumab, methotrexate, cladribine cyclophosphamide or other change in disease modifying therapy (DMT) within 6 months of initiation of study.
• Subjects with any history of cytopenia.
• History of pulmonary obstruction or emphysema.
• Active hepatitis B or hepatitis C infection or evidence of cirrhosis.
• Human immunodeficiency virus (HIV) positivity.
• Uncontrolled diabetes mellitus defined as HbA1c\>8% and/or requiring intensive management.
• Uncontrolled viral, fungal, or bacterial infection (excluding asymptomatic bacteriuria).
• Any condition that, in the opinion of the investigators, would jeopardize the ability of the subject to tolerate treatment with ACZ.
• Prior history of malignancy.

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

UTHealth

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis; Nerve Degeneration

Interventions

Acetazolamide

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: John A. Lincoln, MD, PhD
• Organization: The University of Texas Health Science Center at Houston

John.A.Lincoln@uth.tmc.edu

713-500-7016

Study Officials

• John Lincoln, MD, PhD

  UTHealth

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Two phase design: phase 1, patients randomized to ACZ or placebo and followed for 24 weeks; phase 2, patients that received placebo in phase 1 switch to ACZ (delayed-start group) and patients that received ACZ in phase 1 continue on ACZ (ACZ-ACZ group)

Study Record Dates

• First Submitted: June 3, 2015
• First Posted: June 9, 2015
• Study Start: August 17, 2016
• Primary Completion: February 7, 2022
• Study Completion: February 7, 2022
• Last Updated: April 27, 2023
• Results First Posted: March 1, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)