High-Dose Vitamin C in G6PDA and Pyruvate Kinase Deficiency: A Safety Study (G6PDA PKD)

May 22, 2026 updated by: Jihyun Song, University of Utah

Safety and Tolerability of Supratherapeutic Vitamin C Supplementation in Class A Glucose-6-Phosphate Dehydrogenase (G6PD A) Deficiency and Pyruvate Kinase Deficiency (PKD)

This study is testing whether high-dose Vitamin C is safe and well-tolerated in patients with two inherited red blood cell disorders - Pyruvate Kinase Deficiency (PKD) and Class A Glucose-6-Phosphate Dehydrogenase Deficiency (G6PDA). Both conditions cause red blood cells to break down too quickly, leading to anemia and related complications.

Our earlier research showed that a single oral dose of Vitamin C (250 mg, 500 mg, or 750 mg) reduced red blood cell breakdown by approximately 50% within one hour. This study builds on those findings by testing different doses and frequencies of Vitamin C to find the safest and most effective dosing schedule.

Participants will take Vitamin C once, twice, or three times daily over a 3-week period, with careful monitoring of blood counts, red blood cell survival, iron levels, and any side effects. The study will first enroll 3 adult patients with PKD at Huntsman Cancer Institute. If the results are safe and promising, the study will be extended to patients with G6PDA deficiency, and eventually to children ages 4 and older at Primary Children's Hospital in Salt Lake City.

The goal is to establish a foundation for Vitamin C as a novel therapy to reduce anemia and red blood cell destruction in these rare inherited disorders.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Pyruvate kinase deficiency (PKD) and Class A Glucose-6-Phosphate Dehydrogenase deficiency (G6PDA) are inherited red blood cell enzyme disorders characterized by chronic hemolytic anemia. Current treatment options are limited and do not fully address the underlying mechanisms of red blood cell destruction, iron overload, and oxidative stress.

Our preliminary studies demonstrated that oral Vitamin C administration at doses of 250 mg, 500 mg, and 750 mg reduced the rate of hemolysis by approximately 50% within one hour of administration, as measured by end-tidal carbon monoxide corrected for ambient CO (ETCOc) - a validated marker of red blood cell breakdown. These findings provide a strong rationale for evaluating the safety and optimal dosing frequency of Vitamin C supplementation in these patient populations.

Study Design:

This is a Phase I, single-site, sequential within-patient dose escalation study. Three adult PKD patients will be enrolled in the initial cohort, each assigned to a different starting dose:

Patient 1: 250 mg daily → 250 mg twice daily → 250 mg three times daily Patient 2: 500 mg daily → 500 mg twice daily → 500 mg three times daily Patient 3: 750 mg daily → 750 mg twice daily → 750 mg twice daily + 500 mg once daily (to reach the NIH-recommended maximum daily dose of 2,000 mg/day)

Each dosing frequency will be maintained for one week, for a total active treatment period of 3 weeks per participant. Safety and hematologic assessments will be performed at baseline and at each dose adjustment visit (9 assessments per participant).

Assessments:

At each visit, participants will undergo:

ETCOc measurement to assess real-time hemolysis Complete blood count and reticulocyte count Metabolic panel including bilirubin and LDH Iron studies including serum iron, transferrin, ferritin, hepcidin, and erythroferrone Vital signs and adverse event assessment

Study Extension:

Following successful completion of the PKD cohort, the study will be extended to G6PDA patients, including 5 G6PDA males and 5 G6PDA heterozygous females from a well-characterized family. A subsequent extension to pediatric patients ages 4 and older is planned at Primary Children's Hospital in Salt Lake City, pending safety and preliminary efficacy data from the adult cohort.

Study Type

Interventional

Enrollment (Estimated)

3

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Confirmed diagnosis of Pyruvate Kinase Deficiency (PKD) or Class A glucose-6-phosphate dehydrogenase (G6PD A) as verified by genetic mutation documentation or enzymatic testing
  • 18 years of age or older
  • Able to take oral medications either by mouth or via gastrostomy tube
  • Willing and able to provide written informed consent prior to any study procedures
  • Heterozygous female carrier of G6PDA deficiency

Exclusion Criteria:

  • Does not have an established diagnosis of Pyruvate Kinase Deficiency (PKD) or Class A Glucose-6-Phosphate Dehydrogenase Deficiency (G6PDA)
  • Unable to tolerate oral medications either by mouth or gastrostomy tube
  • Currently pregnant or planning to become pregnant during the study period
  • Incarcerated individuals
  • Unable to provide written informed consent or assent
  • Known allergy or hypersensitivity to Vitamin C (ascorbic acid)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low Dose Vitamin C (250 mg)
Participants receive oral Vitamin C at 250 mg once daily during Week 1, 250 mg twice daily during Week 2, and 250 mg three times daily during Week 3
Drug: Vitamin C
Oral pharmacological grade Vitamin C (Ascorbic Acid) administered at escalating doses and frequencies over a 3-week period. Three dose levels are evaluated: 250 mg, 500 mg, and 750 mg, administered once daily (QD), twice daily (BID), or three times daily (TID) depending on the assigned arm. The maximum daily dose does not exceed 2,000 mg/day, consistent with the NIH-recommended maximum daily dose.
Experimental: Medium Dose Vitamin C (500 mg)
Participants receive oral Vitamin C at 500 mg once daily during Week 1, 500 mg twice daily during Week 2, and 500 mg three times daily during Week 3
Drug: Vitamin C
Oral pharmacological grade Vitamin C (Ascorbic Acid) administered at escalating doses and frequencies over a 3-week period. Three dose levels are evaluated: 250 mg, 500 mg, and 750 mg, administered once daily (QD), twice daily (BID), or three times daily (TID) depending on the assigned arm. The maximum daily dose does not exceed 2,000 mg/day, consistent with the NIH-recommended maximum daily dose.
Experimental: High Dose Vitamin C (750 mg)
Participants receive oral Vitamin C at 750 mg once daily during Week 1, 750 mg twice daily during Week 2, and 750 mg twice daily plus 500 mg once daily during Week 3, to reach the NIH-recommended maximum daily dose of 2,000 mg/day
Drug: Vitamin C
Oral pharmacological grade Vitamin C (Ascorbic Acid) administered at escalating doses and frequencies over a 3-week period. Three dose levels are evaluated: 250 mg, 500 mg, and 750 mg, administered once daily (QD), twice daily (BID), or three times daily (TID) depending on the assigned arm. The maximum daily dose does not exceed 2,000 mg/day, consistent with the NIH-recommended maximum daily dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Dose-Limiting Toxicities (DLTs)
Time Frame: From first dose of study intervention through the 28-day safety follow-up visit (approximately 7 weeks per participant)
Number of participants experiencing Grade 3 or higher adverse events as defined by NCI CTCAE v5.0 that are possibly, probably, or definitely related to oral Vitamin C administration at each dose level (250 mg, 500 mg, and 750 mg) and dosing frequency (once daily, twice daily, and three times daily). Hematologic DLTs include Grade ≥3 hemolysis above patient baseline, Grade ≥3 anemia (hemoglobin <8 g/dL), Grade 4 neutropenia (ANC <0.5 × 10⁹/L), and Grade 4 thrombocytopenia (platelet count <25 × 10⁹/L). Non-hematologic DLTs include Grade 3 acute kidney injury, Grade 3 ALT or AST elevation, and any other Grade 3 or higher toxicity considered related to study intervention.
From first dose of study intervention through the 28-day safety follow-up visit (approximately 7 weeks per participant)
Number of Participants With Treatment-Related Adverse Events as Assessed by NCI CTCAE v5.0
Time Frame: From first dose of study intervention through the 28-day safety follow-up visit (approximately 7 weeks per participant)
Incidence and severity of all adverse events reported during the study, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0), including all adverse events possibly, probably, or definitely related to oral Vitamin C administration.
From first dose of study intervention through the 28-day safety follow-up visit (approximately 7 weeks per participant)
Change in Hemoglobin Concentration from Baseline
Time Frame: Baseline (Day 1) through Week 3 of treatment and 28-day safety follow-up visit
Change in hemoglobin concentration from baseline to each dose adjustment visit, measured by complete blood count (CBC).
Baseline (Day 1) through Week 3 of treatment and 28-day safety follow-up visit
Change in Reticulocyte Count from Baseline
Time Frame: Baseline (Day 1) through Week 3 of treatment and 28-day safety follow-up visit
Change in reticulocyte count from baseline to each dose adjustment visit, measured by complete blood count (CBC).
Baseline (Day 1) through Week 3 of treatment and 28-day safety follow-up visit
Change in Lactate Dehydrogenase (LDH) from Baseline
Time Frame: Baseline (Day 1) through Week 3 of treatment and 28-day safety follow-up visit
Change in serum LDH levels from baseline to each dose adjustment visit as a marker of hemolysis.
Baseline (Day 1) through Week 3 of treatment and 28-day safety follow-up visit
Change in Systolic Blood Pressure from Baseline
Time Frame: Baseline (Day 1) through Week 3 of treatment and 28-day safety follow-up visit
Change in systolic blood pressure from baseline to each study visit as part of vital signs assessment.
Baseline (Day 1) through Week 3 of treatment and 28-day safety follow-up visit
Change in Heart Rate from Baseline
Time Frame: Baseline (Day 1) through Week 3 of treatment and 28-day safety follow-up visit
Change in heart rate from baseline to each study visit as part of vital signs assessment.
Baseline (Day 1) through Week 3 of treatment and 28-day safety follow-up visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Utah

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 15, 2026

Primary Completion (Estimated)

July 15, 2027

Study Completion (Estimated)

December 15, 2027

Study Registration Dates

First Submitted

May 19, 2026

First Submitted That Met QC Criteria

May 22, 2026

First Posted (Actual)

May 28, 2026

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 22, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 00187727

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data will be made available upon reasonable request following publication of study results. Data will be stored securely at the Huntsman Cancer Institute and shared in accordance with applicable IRB and institutional data sharing policies.

IPD Sharing Time Frame

Beginning 6 months after primary results publication and available for 5 years thereafter

IPD Sharing Access Criteria

Researchers may submit data access requests to the Principal Investigator (Jihyun Song, PhD) at jihyun.song@utah.edu. Requests will be reviewed on a case-by-case basis.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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