Acetazolamide Efficacy in Ataxia in PMM2-CDG
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|ClinicalTrials.gov Identifier: NCT04679389|
Recruitment Status : Active, not recruiting
First Posted : December 22, 2020
Last Update Posted : May 16, 2023
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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.
|Condition or disease||Intervention/treatment||Phase|
|Pmm2-CDG CDG1A||Drug: Placebo Drug: Acetazolamide||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||26 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Randomized, double blind, placebo controlled, with optional extension period|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Double blind|
|Official Title:||A Randomized, Double-blind, Placebo-controlled Study Evaluating Acetazolamide Efficacy in Ataxia in PMM2-CDG|
|Actual Study Start Date :||March 17, 2021|
|Estimated Primary Completion Date :||January 2024|
|Estimated Study Completion Date :||January 2024|
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
administered orally or enterally
Other Name: Diamox
Placebo Comparator: Placebo
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.
administered orally or enterally
Other Name: Gelatin, lactose, and Ora-blend
- Efficacy of Acetazolamide on ataxia measured via Miniature International Cooperative Ataxia Rating Scale (mini-ICARS) [ Time Frame: baseline-6 months ]To achieve this goal, we will compare 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.
- Percentage of participants with assessed adverse events of long term acetazolamide administration as seen on blood pH value [ Time Frame: through study completion, an average of three years ]Blood pH level will be assessed through venous blood gas test. Percentage of patients treated with Acetazolamide who experience a drug related adverse event related to abnormal blood pH value.
- Percentage of participants with assessed adverse events of long term acetazolamide administration as seen on electrolyte balance testing [ Time Frame: through study completion, an average of three years ]Electrolyte balance will be assessed through combination testing on concentration of potassium, sodium, chloride, bicarbonate, magnesium, calcium, and phosphate. Percentage of patients treated with Acetazolamide who experience a drug related adverse event related to abnormal electrolyte balance.
- Percentage of participants with assessed adverse events of long term acetazolamide administration as seen on urine calcium excretion testing. [ Time Frame: through study completion, an average of three years ]Urine calcium excretion is measured by mg excreted per day. Percentage of patients treated with Acetazolamide who experience a drug related adverse event related to abnormal excretion of calcium.
- Examine effect of Acetazolamide on PMM2 biomarker carbohydrate deficient transferrin [ Time Frame: baseline and 6 months ]Carbohydrate deficient transferrin is reported by ratio. Number of patients with abnormal ratio result will be recorded to understand the effect acetazolamide has on this biomarker
- Examine effect of Acetazolamide on Patient Reported Outcomes Measuremen Information System (PROMIS) Score [ Time Frame: baseline and 6 months ]PROMIS score measures physical activity, strength impact, fatigue, mobility, pain interference, upper extremity coordination, global health, mobility, anxiety, depression, peer relationships, and pain intensity. These are patient reported scores. Higher score means more or the concept being measured (example: high score on Fatigue scale means high level of fatigue).
- Examine effect of Acetazolamide on dysarthria as measured by the PATA score [ Time Frame: baseline and 6 months ]PATA test measures the number of times a patient can say the word "PATA" in a 10 second time period. Number of "PATA"s spoken in 10 seconds indicates level of dysarthria.
- Examine effect of Acetazolamide on disease progression as measured by the Nijmegen Pediatric CDG Rating Scale (NPCRS) [ Time Frame: baseline and 6 months ]The NPCRS is a scale that evaluates the patient's current function, system specific involvement, and current clinical assessment. A mild score is 0-14, moderate score is 15-25, and severe is a score >26.
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|Ages Eligible for Study:||4 Years and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04679389
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Washington|
|Seattle Children's Hospital|
|Seattle, Washington, United States, 98105|
|Principal Investigator:||Eva Morava-Kozicz, MD, PhD||Mayo Clinic|
|Responsible Party:||Eva Morava-Kozicz, Principal Investigator, Mayo Clinic|
|Other Study ID Numbers:||
|First Posted:||December 22, 2020 Key Record Dates|
|Last Update Posted:||May 16, 2023|
|Last Verified:||May 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Plan Description:||De-identified data may be shared amongst member of the consortium FCDGC and with the NIH.|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||No|
Congenital Disorders of Glycosylation
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Carbonic Anhydrase Inhibitors
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs