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

NCT07612345 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 00187727
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pyruvate Kinase Deficiency; Glucose 6 Phosphate Dehydrogenase Deficiency

Keywords

Pyruvate Kinase Deficiency, Glucose-6-Phosphate Dehydrogenase Deficiency, Antioxidant, Vitamin C, Hemolytic Anemia

Outcome Measures

Primary Outcomes (7)

• Incidence of Dose-Limiting Toxicities (DLTs)

  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

  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

  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

  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

  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

  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

  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

Study Arms (3)

Low Dose Vitamin C (250 mg)

EXPERIMENTAL

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

Medium Dose Vitamin C (500 mg)

EXPERIMENTAL

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

High Dose Vitamin C (750 mg)

EXPERIMENTAL

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

Interventions

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.

High Dose Vitamin C (750 mg); Low Dose Vitamin C (250 mg); Medium Dose Vitamin C (500 mg)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (17)

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MeSH Terms

Conditions

Pyruvate Kinase Deficiency of Red Cells; Glucosephosphate Dehydrogenase Deficiency; Anemia, Hemolytic

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Central Study Contacts

Jihyun Song, PhD

CONTACT

801-587-4682; jihyun.song@utah.edu

Josef T. Prchal, MD

CONTACT

801-213-6013; josef.prchal@hsc.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Assistant Professor

Study Record Dates

• First Submitted: May 19, 2026
• First Posted: May 28, 2026
• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): July 15, 2027
• Study Completion (Estimated): December 15, 2027
• Last Updated: May 28, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Beginning 6 months after primary results publication and available for 5 years thereafter
• 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.

Locations

US (1)