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NCT Number: NCT07612345

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

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.

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Key information

Conditions

Pyruvate Kinase Deficiency Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Glucose 6 Phosphate Dehydrogenase Deficiency Glucosephosphate Dehydrogenase Deficiency Hematologic Diseases Hemic and Lymphatic Diseases Metabolic Diseases Metabolism, Inborn Errors Nutritional and Metabolic Diseases Pyruvate Kinase Deficiency of Red Cells

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Vitamin C

Drug

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.

Primary outcomes

  1. 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.

  2. 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.

  3. 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).

  4. 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).

  5. 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.

  6. 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.

  7. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Jihyun Song, PhD

CONTACT

[email protected]

801-587-4682

Josef T. Prchal, MD

CONTACT

[email protected]

801-213-6013

Sponsors and collaborators

Lead sponsor

University of Utah

Other

Registry information

Official study title

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

Acronym: G6PDA PKD

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
May 28, 2026
Registry last updated
May 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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