Acetazolamide Efficacy in Ataxia in PMM2-CDG

NCT04679389 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 20-000634
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

Brief Summary

Objective 1 (Primary): To determine the efficacy of acetazolamide in improving ataxia in patients with PMM2-CDG. Objective 2 (Secondary): To evaluate for any adverse events related to longer term acetazolamide administration. Objective 3 (Secondary): To examine the effect of acetazolamide on PMM2 biomarkers including carbohydrate deficient transferrin results, electrolytes (Na, K, Cl, CO2), VBG (pH, pCO2, PO2, CO2, Base excess), liver function tests (AST, ALT, GGT, indirect and direct bilirubin, total protein, albumin, alkaline phosphatase), kidney function tests (BUN, Creatinine, Urinalysis, urine calcium/creatinine ratio, urine protein/creatinine ratio), growth (height, weight, head circumference), vital signs (blood pressure, respiratory rate, heart rate), PROMIS scores, dysarthria using the PATA score, and NPCRS score. Objective 4 (Secondary): To explore characteristics of individuals with PMM2-CDG who do not respond to acetazolamide.

Conditions

Pmm2-CDG; CDG1A

Outcome Measures

Primary Outcomes (1)

• Efficacy of Acetazolamide on Ataxia Measured Via Miniature International Cooperative Ataxia Rating Scale (Mini-ICARS)

  To achieve this goal, we compared the change of Mini-ICARS score from baseline to after six months of treatment between the placebo and active treatment groups. Minimal score is 0, maximum score is 100, higher score indicates greater impairment. Each subscale has an ordinal scale with a 0 indicating normal and the higher score indicating greater impairment or that the patient was unable to complete the task.

  baseline-6 months

Secondary Outcomes (7)

• Abnormal Blood pH Value

  through study completion, approximately 2 years

• Electrolyte Balance Testing

  through study completion, approximately 2 years

• Urine Calcium Excretion Testing

  through study completion, approximately 2 years

• Examine Effect of Acetazolamide on PMM2 Biomarker Carbohydrate Deficient Transferrin

  6 months

• Change in Patient Reported Outcomes Measurement Information System (PROMIS) Score

  baseline, 6 months

Study Arms (2)

Acetazolamide

EXPERIMENTAL

Acetazolamide administered via capsule or liquid suspension. Capsule would be 250 mg oral capsules encapsulated by gelatin capsule and filled with lactose to match placebo. Liquid suspension would be 25 mg/mL oral suspension but adding 125 mg Acetazolamide tablets to suspending agent Ora-blend

Drug: Acetazolamide

Placebo

PLACEBO COMPARATOR

Placebo administered via capsule or liquid suspension. Capsule would be a gelatin capsule filled with lactose powder to match Acetazolamide. Liquid suspension would be Ora-blend.

Drug: Placebo

Interventions

Placebo DRUG

administered orally or enterally

Also known as: Gelatin, lactose, and Ora-blend

Placebo

Acetazolamide DRUG

administered orally or enterally

Also known as: Diamox

Acetazolamide

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Molecularly and/or enzymatically-confirmed PMM2-CDG,
• Age ≥4 years old, and
• Affected with ataxia evidenced by mini International Cooperative Ataxia Rating Scale (Mini-ICARS) score \>0 at baseline.

You may not qualify if:

• Hepatic impairment defined as AST/ALT \>5x ULN in the last 12 months
• Renal impairment defined as serum creatinine: \> 0.5 mg/dL (\<6 years); \> 0.7 mg/dL (7-10 years); \> 1.24 mg/dL (\> 11 years)- Hypersensitivity to acetazolamide
• Hypersensitivity to any of the components of the placebo
• History of treatment with experimental drug within 28 days of Visit 1
• Currently taking Mecamylamine, Sodium Phosphates, Salicylates, Mefloquine, Methenamine and other Carbonic Anhydrase Inhibitors

Sponsors & Collaborators

• Mayo Clinic: lead
• Seattle Children's Hospital: collaborator
• Children's Hospital of Philadelphia: collaborator

Study Sites (3)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Congenital disorder of glycosylation type 1A

Interventions

Gelatin; Lactose; Acetazolamide

Intervention Hierarchy (Ancestors)

Scleroproteins; Proteins; Amino Acids, Peptides, and Proteins; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars; Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Eva Morava-Kozicz, M.D., Ph.D.
• Organization: Mayo Clinic

Morava-Kozicz.Eva@mayo.edu

507-266-9140

Study Officials

• Eva Morava-Kozicz, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized, double blind, placebo controlled, with optional extension period

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: December 22, 2020
• Study Start: March 17, 2021
• Primary Completion: January 24, 2024
• Study Completion: January 24, 2024
• Last Updated: March 20, 2025
• Results First Posted: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)