Clinical trial NCT01833351: Evaluation of Intravenous Ascorbic Acid
Official title: Pharmacokinetic Evaluation of Intravenous Ascorbic Acid
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Safety and Pharmacokinetics of Intravenous Ascorbate
Keywords: Phase I
safety and pharmacokinetics,
intravenous ascorbate,
IV Vitamin C,
Oncology
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: Thomas Jefferson University
First posted: 2013-04-16
Enrollment: 34
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This Phase I study will be conducted in 2 parts to examine safety and pharmacokinetics of escalating doses of intravenous ascorbic acid (AA) first in healthy volunteers followed by evaluation in oncology subjects. The study will be conducted in the Program in Integrative Medicine Infusion Clinic at the University of Kansas Medical Center in conjunction with the Program in Integrative Medicine, Kansas Cancer Research Institute, Department of Pharmacy, Department of Medical Oncology, the Division of Surgical Oncology,and with consultants from the NIH, and FDA.

Detailed description: The purpose of this study is to examine what happens when Vitamin C enters into the body, and the speed and ways it travels through the body, and the rate at which it exits the body in the urine. It is also necessary to determine if it is safe to give Intravenous Vitamin C at high doses.

Eligibility criteria: PART 1 ELIGIBILITY CRITERIA

Inclusion:

* Healthy adults age 21 or older
* Laboratory: ANC ≥1,500/mm3,

  * Hemoglobin \> 8g/dL,
  * platelet ≥ 100,000/mm3,
  * total bilirubin ≤ 1.5 mg/dL,
  * creatinine ≤2.0 mg/dL,
  * transaminase (AST/ALT) ≤2.5X upper limit,
  * urine uric acid \< 1,000mg/d,
  * urine pH \<6,
  * urine oxalate \<60 mg/d.
* Participants who have no language barrier, are cooperative, and can give informed consent before entering the study after being informed of the medications and procedures to be used in this study may participate.

Exclusion:

* Glucose-6-phosphate-dehydrogenase (G6PD) deficiency
* History of bleeding disorder
* History of oxalate renal calculi; urine oxalate level \> 60 mg/d at baseline
* History of iron overload or hemochromatosis
* Participants with evidence of a significant psychiatric disorder by history/examination that would prevent completion of the study will not be allowed to participate.
* Co-morbid condition that would affect survival: end stage congestive heart failure, unstable angina, myocardial infarction within 6 weeks of study, uncontrolled blood sugars ≥ 300 mg/dL, participants with known chronic active hepatitis or cirrhosis.
* Participants who consume an excess of alcohol or abuse drugs (an excess of alcohol is defined as more than four of any one of the following per day: 30mL distilled spirits, 340mL beer, or 120mL wine) will not be allowed.
* Participants who smoke tobacco products will not be allowed to participate.

PART 2 ELIGIBILITY CRITERIA

Inclusion:

* Oncology participants must have histologically or cytologically diagnosed malignancy.
* The oncology participants must be age 21 or older and screened for eligibility and have study approved by treating oncologist.
* Oncology participants must be unwilling or ineligible for further radiation or chemotherapy at the time of enrollment into study.
* Participants must be without evidence of active spinal cord compression and have predicted lifespan of 6-months or more.
* ECOG Performance Status 0-2

  * Eastern Cooperative Oncology Group Performance Status
  * Grade 0 = Fully active, able to carry on all pre-disease activities without restriction
  * Grade 1= Restricted in physical strenuous activity but ambulatory and able to carry out work of a light or sedentary nature e.g. light housework, office work
  * Grade 2 = Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours.
* Laboratory:

  * ANC ≥1,500/mm3,
  * Hemoglobin \> 8g/dL,
  * platelet ≥ 100,000/mm3,
  * total bilirubin ≤ 1.5 mg/dL,
  * creatinine ≤2.0 mg/dL,
  * transaminase (AST/ALT) ≤2.5X upper limit,
  * urine uric acid \< 1,000mg/d, urine pH \<6,
  * urine oxalate \<60 mg/d.
* Participants who have no language barrier, are cooperative, and can give informed consent before entering the study after being informed of the medications and procedures to be used in this study may participate.

Exclusion:

* Glucose-6-phosphate-dehydrogenase (G6PD) deficiency
* Currently receiving chemotherapy or radiation therapy
* History of bleeding disorder
* History of oxalate renal calculi; urine oxalate level \> 60 mg/d at baseline
* History of iron overload or hemochromatosis
* Participants with evidence of a significant psychiatric disorder by history/examination that would prevent completion of the study will not be allowed to participate.
* ECOG Performance Status of 3-4

  * Grade 3 = Capable of only limited self care, confined to bed or chair more than 50% of waking hours.
  * Grade 4 = Completely disabled. Cannot carry on any self care. Totally confined to bed or chair) and in terminal stages of disease.
* Co-morbid condition that would affect survival: end stage congestive heart failure, unstable angina, myocardial infarction within 6 weeks of study, uncontrolled blood sugars ≥ 300 mg/dL, participants with known chronic active hepatitis or cirrhosis.
* Those who consume an excess of alcohol or abuse drugs (an excess of alcohol is defined as more than four of any one of the following per day: 30mL distilled spirits, 340mL beer, or 120mL wine) will not be allowed.
* Those who smoke tobacco products will not be allowed to participate.

Primary outcomes:
measure: identify the maximum tolerated dose (MTD)
timeFrame: Change from infusion to 24 hours past infusion
Secondary outcomes:
measure: measure how the body absorbs, distributes and excretes intravenous ascorbic acid
timeFrame: 0,.5,1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 24 hours post-dose
measure: measure the biochemical and physiological effects of intravenous ascorbic
timeFrame: 0,.5,1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 24 hours post-dose
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: University of Kansas Medical Center
name: Jeanne Drisko, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen P, Reed G, Jiang J, Wang Y, Sunega J, Dong R, Ma Y, Esparham A, Ferrell R, Levine M, Drisko J, Chen Q. Pharmacokinetic Evaluation of Intravenous Vitamin C: A Classic Pharmacokinetic Study. Clin Pharmacokinet. 2022 Sep;61(9):1237-1249. doi: 10.1007/s40262-022-01142-1. Epub 2022 Jun 25.