Pmm2-CDGPhase 2/3NCT04679389
Acetazolamide Efficacy in Ataxia in PMM2-CDG
A Phase 2/3 study testing Acetazolamide in people with Pmm2-CDG and CDG1A, run by Mayo Clinic at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 years and older
- What is being tested?
- Acetazolamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 3 sitesUnited States
- Study dates
- 17 Mar 2021to 24 Jan 2024
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Rochester, Minnesota, 55905
Seattle Children's Hospital
Seattle, Washington, 98105
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Study Evaluating Acetazolamide Efficacy in Ataxia in PMM2-CDG
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.
Read more
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.
Read the detailed description
This study is double-blind, placebo-controlled, 1:1 randomized clinical therapeutic trial of acetazolamide for the treatment of ataxia in patients with PMM2-CDG. Clinical history and screening data will be reviewed to determine subject eligibility. Potential subjects who have a molecularly and/or biochemical confirmed diagnosis of PMM2-CDG will be consented. Baseline data will be collected prior to randomization and at treatment initiation. Subjects who meet all inclusion criteria and none of the exclusion criteria will be enrolled into the study. Each subject who meets all the inclusion and none of the exclusion criteria will then be randomized to placebo or acetazolamide. They will be administered weight-dependent doses of acetazolamide or an equivalent volume of placebo twice daily by mouth. Initial dose of acetazolamide is 8 mg/kg/day if subjects are taking the liquid formulation, or as per Table 1b if they are taking the capsule formulation. If taking the liquid formulation, the dose of study drug will be increased by 7 mg/kg/day to a maximum of 22 mg/kg/day (not to exceed 1000 mg/day) if well tolerated with no treatment related SAEs or abnormal pH. If the pH is <7.32, the dose will be reduced by 7 mg/kg/day. The dose will be adjusted similarly according to Table 1b if taking the capsule formulation. Subjects will be randomized after Visit 1, will initiate blinded therapy within the first week, and will continue on prescribed/adjusted blinded treatment until Visit 4. Of note, the concentration of the liquid formulation and the amount of milligrams of acetazolamide per capsule will stay constant, and the volume or number of capsules will be adjusted based on tolerance as assessed by symptoms and laboratories. If an individual is randomized to the placebo arm, the initial volume will be equivalent to 7 mg/kg/day or the initial number of capsules as per Table 1, and volume or number of capsules will also be adjusted based on symptoms and laboratory values each time dose adjustment is planned. Open label period will then begin after Visit 4 up to Visit 9 (see Figure 1 and Table 3). As both the subject and investigator do not know if the subject received placebo or acetazolamide, the dose of acetazolamide will be started at Visit 4 at 8 mg/kg/day and titrated upwards in the same manner in Visits 5 and 6 (remote) as in Visits 2 and 3 (remote). Subjects will have the option to withdraw from the study any time after Visit 4 if they do not wish to proceed onto or continue with the open label phase.
- Being tested
- Placebo, Acetazolamide
- Medical subject headings
- Congenital disorder of glycosylation type 1A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Also called Gelatin, lactose, and Ora-blend
administered orally or enterally
AcetazolamideDrug
Also called Diamox
administered orally or enterally
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline-6 months
Secondary outcomes (7)
Abnormal Blood pH Value
Blood pH level was assessed through venous blood gas test. The number of participants who experience a drug related adverse event related to abnormal blood pH value.
Measured: through study completion, approximately 2 years
Electrolyte Balance Testing
Electrolyte balance was assessed through combination testing on concentration of potassium, sodium, chloride, bicarbonate, magnesium, calcium, and phosphate. The number of participants who experience a drug related adverse event related to abnormal electrolyte balance.
Measured: through study completion, approximately 2 years
Urine Calcium Excretion Testing
Urine calcium excretion is measured by mg excreted per day. The number of participants who experience a drug related adverse event related to abnormal excretion of calcium.
Measured: through study completion, approximately 2 years
Examine Effect of Acetazolamide on PMM2 Biomarker Carbohydrate Deficient Transferrin
Number of patients with abnormal ratio result will be recorded to understand the effect acetazolamide has on this biomarker
Measured: 6 months
Change in Patient Reported Outcomes Measurement Information System (PROMIS) Score
PROMIS = Physical activity 10-items from 1(no days) to 5(6-7 days), Strength impact 12-item from 1(no days) to 5(6-7 days), Fatigue 23-item from 1(never) to 5(almost always), Mobility 23-item from 1(not able to do) to 5(with no trouble), Pain interference 13-item from 1(never) to 5(almost always), Upper extremity coordination 29-item from 1(not able to do) to 5(with no trouble), Global Health 9-item from 1(poor) to 5( excellent), Parent Proxy Mobility 8-item from 1(not able to do) to 5(with no trouble), Anxiety 8-item from 1(never) to 5(almost always), Depresson 8-item from 1(never) to 5(almost always), Parent Proxy Fatigue 8-item from 1(never) to 5(almost always), Peer relationships 8-item from 1(never) to 5(almost always), Parent proxy pain interference 8-item from 1(never) to 5(almost always), Pain intensity 1-item from 0(no pain) to 10(worst pain). Total scores range from 168 - 845. Lower scores indicate worse health, higher scores indicate better health
Measured: baseline, 6 months
Change in Dysarthria as Measured by the PATA Score
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. The higher the score the less dysarthria, the lower the score more dysarthria.
Measured: baseline, 6 months
Change in Nijmegen Pediatric CDG Rating Scale (NPCRS)
The NPCRS is a scale that evaluates the patient's current function, system specific involvement, and current clinical assessment. Total scores range from 0 - 82. A mild score is 0-14, moderate score is 15-25, and severe is a score >26.
Measured: baseline, 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2020
- Study start17 Mar 2021
- Primary completion24 Jan 2024
- Study completion24 Jan 2024
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pmm2-CDGStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double blind, placebo controlled, with optional extension period
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eva Morava-Kozicz, Mayo Clinic
- Investigators
- Eva Morava-Kozicz, MD, PhD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04679389
- Sponsor's protocol ID
- 20-000634
- Status last verified
- Mar 2025
- First submitted
- 14 Dec 2020
- Last updated
- 20 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: De-identified data may be shared amongst member of the consortium FCDGC and with the NIH.
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Study Evaluating Acetazolamide Efficacy in Ataxia in PMM2-CDG
- ClinicalTrials.gov ID
- NCT04679389
- Acronym / sponsor ID
- 20-000634
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Seattle Children's Hospital, Children's Hospital of Philadelphia
- Study start
- 17 Mar 2021 (actual)
- Primary completion
- 24 Jan 2024 (actual)
- Study completion
- 24 Jan 2024 (actual)
- First posted
- 22 Dec 2020 (actual)
- Results
- Posted 20 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study is double-blind, placebo-controlled, 1:1 randomized clinical therapeutic trial of acetazolamide for the treatment of ataxia in patients with PMM2-CDG. Clinical history and screening data will be reviewed to determine subject eligibility. Potential subjects who have a molecularly and/or biochemical confirmed diagnosis of PMM2-CDG will be consented. Baseline data will be collected prior to randomization and at treatment initiation. Subjects who meet all inclusion criteria and none of the exclusion criteria will be enrolled into the study. Each subject who meets all the inclusion and none of the exclusion criteria will then be randomized to placebo or acetazolamide. They will be administered weight-dependent doses of acetazolamide or an equivalent volume of placebo twice daily by mouth. Initial dose of acetazolamide is 8 mg/kg/day if subjects are taking the liquid formulation, or as per Table 1b if they are taking the capsule formulation. If taking the liquid formulation, the dose of study drug will be increased by 7 mg/kg/day to a maximum of 22 mg/kg/day (not to exceed 1000 mg/day) if well tolerated with no treatment related SAEs or abnormal pH. If the pH is <7.32, the dose will be reduced by 7 mg/kg/day. The dose will be adjusted similarly according to Table 1b if taking the capsule formulation. Subjects will be randomized after Visit 1, will initiate blinded therapy within the first week, and will continue on prescribed/adjusted blinded treatment until Visit 4. Of note, the concentration of the liquid formulation and the amount of milligrams of acetazolamide per capsule will stay constant, and the volume or number of capsules will be adjusted based on tolerance as assessed by symptoms and laboratories. If an individual is randomized to the placebo arm, the initial volume will be equivalent to 7 mg/kg/day or the initial number of capsules as per Table 1, and volume or number of capsules will also be adjusted based on symptoms and laboratory values each time dose adjustment is planned. Open label period will then begin after Visit 4 up to Visit 9 (see Figure 1 and Table 3). As both the subject and investigator do not know if the subject received placebo or acetazolamide, the dose of acetazolamide will be started at Visit 4 at 8 mg/kg/day and titrated upwards in the same manner in Visits 5 and 6 (remote) as in Visits 2 and 3 (remote). Subjects will have the option to withdraw from the study any time after Visit 4 if they do not wish to proceed onto or continue with the open label phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double blind, placebo controlled, with optional extension period
| Arm | Type | Receives |
|---|---|---|
| Acetazolamide | Experimental | Drug: AcetazolamideAcetazolamide 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 |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAlso: Gelatin, lactose, and Ora-blendadministered orally or enterally | Drug | Placebo |
| AcetazolamideAlso: Diamoxadministered orally or enterally | Drug | Acetazolamide |
Primary outcome
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 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.
7 secondary outcomes
Abnormal Blood pH Value
Time frame: through study completion, approximately 2 years
Electrolyte Balance Testing
Time frame: through study completion, approximately 2 years
Urine Calcium Excretion Testing
Time frame: through study completion, approximately 2 years
Examine Effect of Acetazolamide on PMM2 Biomarker Carbohydrate Deficient Transferrin
Time frame: 6 months
Change in Patient Reported Outcomes Measurement Information System (PROMIS) Score
Time frame: baseline, 6 months
Change in Dysarthria as Measured by the PATA Score
Time frame: baseline, 6 months
Change in Nijmegen Pediatric CDG Rating Scale (NPCRS)
Time frame: baseline, 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. De-identified data may be shared amongst member of the consortium FCDGC and with the NIH.
Related trials for Pmm2-CDG
Enrolling by invitationPhase 2
Open-Label Extension Study to Assess GLM101 in PMM2-CDG Patients
Pmm2-CDG, Phosphomannomutase 2 Deficiency
Active, not recruitingPhase 2/3
A Study to Assess the Efficacy and Safety of Weekly Doses of GLM101 in Participants With PMM2-CDG
Phosphomannomutase 2 Deficiency, PMM2-CDG
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eva Morava-Kozicz, MD, PhD principal investigator
Mayo Clinic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Acetazolamide in people with Pmm2-CDG and CDG1A, run by Mayo Clinic at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of Acetazolamide on Ataxia Measured Via Miniature International Cooperative Ataxia Rating Scale (Mini-ICARS) (time frame: baseline-6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2025; AzTrials last refreshed its copy on 6 Nov 2026.