Urinary Vitamin C Loss in Diabetic Subjects

• ClinicalTrials.gov Identifier: NCT00071526
• Recruitment Status: Recruiting
• First Posted: October 28, 2003
• Last Update Posted: May 20, 2024
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )

Tracking Information

• First Submitted Date: October 27, 2003
• First Posted Date: October 28, 2003
• Last Update Posted Date: May 20, 2024
• Actual Study Start Date: April 11, 2006
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: September 25, 2019)

Plasma, neutrophil and RBC Vitamin C concentrates [ Time Frame: end of study ]

Measurements of plasma, neutrophil and red blood cell vitamin c concentrations in diabetic subjects as compared to healthy controls.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: May 6, 2021)

• Urinary vitamin C concentration [ Time Frame: end of study ]
  Measurements of urinary vitamin c concentrations in diabetic subjects as compared to healthy controls.
• Determine the renal threshold and relative bioavailability for vitamin C [ Time Frame: end of study ]
  Calculate renal threshold of vitamin C in diabetic subjects as compared to healthy controls.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Urinary Vitamin C Loss in Diabetic Subjects
• Official Title: Urinary Vitamin C Loss in Subjects With and Without Diabetes
• Brief Summary: Several studies have reported that diabetic subjects have lower plasma vitamin C concentrations than non-diabetic subjects. Although urinary vitamin C loss in diabetic subjects was reported to be increased in two studies, these are difficult to interpret due to lack of controlled vitamin C intake, inadequate sampling, lack of control subjects, or methodology uncertainties in vitamin C assay and sample processing. Consequently, it is unclear whether diabetic subjects truly have both low plasma and high urine vitamin C concentrations. We propose that low plasma vitamin C concentrations in diabetic subjects are due in part to inappropriate renal loss of vitamin C in these subjects but not in healthy controls. We will study vitamin C concentrations in patients with type 1 and type 2 diabetes and in matched healthy research subjects. Vitamin C concentrations in plasma, neutrophils (as a proxy for tissue concentrations) and in urine will be measured in outpatients. In those willing to be admitted to the Clinical Center, we will measure 24-hour urinary excretion of vitamin C while on a vitamin C free diet, and creatinine clearance, a measure of glomerular filtration rate. On day 2 of the inpatient study, subjects will receive a single 200mg dose of oral vitamin C and we will measure vitamin C concentrations in frequent blood and urine samples to determine the renal threshold and relative bioavailability for vitamin C. Single nucleotide polymorphisms (SNPs) will be determined in genomic DNA responsible for the two proteins mediating sodium-dependent vitamin C transport, SVCT1 and SVCT2. If low plasma and high urine vitamin C concentrations are found in diabetic subjects, further studies will be needed to explore mechanisms and to determine recommended dietary allowances for this patient population.
• Detailed Description: Several studies have reported that diabetic subjects have lower plasma vitamin C concentrations than non-diabetic subjects. Although urinary vitamin C loss in diabetic subjects was reported to be increased in two studies, these are difficult to interpret due to lack of controlled vitamin C intake, inadequate sampling, lack of control subjects, or methodology uncertainties in vitamin C assay and sample processing. Consequently, it is unclear whether diabetic subjects truly have both low plasma and high urine vitamin C concentrations. We propose that low plasma vitamin C concentrations in diabetic subjects are due in part to inappropriate renal loss of vitamin C in these subjects but not in healthy controls. We will study vitamin C concentrations in patients with type 1 and type 2 diabetes and in matched healthy research subjects. Vitamin C concentrations in plasma, neutrophils (as a proxy for tissue concentrations) and in urine will be measured in outpatients. In those willing to be admitted to the Clinical Center, we will measure 24-hour urinary excretion of vitamin C while on a vitamin C free diet, and creatinine clearance, a measure of glomerular filtration rate. On day 2 of the inpatient study, subjects will receive a single 200mg dose of oral vitamin C and we will measure vitamin C concentrations in frequent blood and urine samples to determine the renal threshold and relative bioavailability for vitamin C. Single nucleotide polymorphisms (SNPs) will be determined in genomic DNA responsible for the two proteins mediating sodium-dependent vitamin C transport, SVCT1 and SVCT2. If low plasma and high urine vitamin C concentrations are found in diabetic subjects, further studies will be needed to explore mechanisms and to determine recommended dietary allowances for this patient population.
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Probability Sample
• Study Population: Community sample.
• Condition: Diabetes
• Intervention: Not Provided

Study Groups/Cohorts

• Diabetes Type I
  Subjects with Type I diabetes mellitus
• Diabetes Type II
  Subjects with Type II diabetes mellitus
• Healthy Volunteers
  Healthy Volunteers

Publications *

• Levine M. New concepts in the biology and biochemistry of ascorbic acid. N Engl J Med. 1986 Apr 3;314(14):892-902. doi: 10.1056/NEJM198604033141407. No abstract available.
• Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy elderly population. JAMA. 1983 Jun 3;249(21):2917-21.
• Fata FT, Herzlich BC, Schiffman G, Ast AL. Impaired antibody responses to pneumococcal polysaccharide in elderly patients with low serum vitamin B12 levels. Ann Intern Med. 1996 Feb 1;124(3):299-304. doi: 10.7326/0003-4819-124-3-199602010-00003.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 6, 2021): 5000
• Original Enrollment (submitted: June 23, 2005): 150
• Study Completion Date: Not Provided
• Primary Completion Date: Not Provided

Eligibility Criteria

• INCLUSION CRITERIA:

We propose to study of five thousand male and female subjects between the ages of 18 and 65. This will include healthy subjects and subjects with type 1 or type 2 diabetes. To be included in the study, study subjects should

• be in good general health
• have no significant illnesses that compromise clinical stability other than the complications of diabetes mellitus alone or in the context of metabolic syndrome. Subjects with ischemic heart disease and/or peripheral artery disease are eligible for arm 1 of the protocol.
• have serum creatinine < 2.5
• for healthy volunteers, be normotensive at the time of the study, with a blood pressure less than or equal to 140/90
• for diabetic subjects, blood pressure less than or equal to 170/95 as long as clinically stable and in usual state of health, for example, no chest pain, shortness of breath, headache, syncope or fatigue

The aim of this study is to determine whether diabetic subjects lose vitamin C in the urine in their normal clinical condition (i.e. while on treatment) and not in the native untreated state of uncontrolled hyperglycemia. Therefore the patients will not discontinue medication.

EXCLUSION CRITERIA (for arm 1):

Exclusion criteria will include the following:

• significant organ malfunction leading to clinical instability including liver disease, pulmonary disease, stroke and anemia at investigator discretion
• serious or chronic illness or history of serious or chronic illness resulting in clinical instability other than complications of diabetes
• pregnancy
• alcohol abuse, drug addiction or the use of illegal drugs
• positive HIV or hepatitis (B or C) screening tests (subjects will be notified of these test results).
• presence of other concomitant conditions which in the judgment of the investigators can influence vitamin C metabolism or vitamin C renal handling

EXCLUSION CRITERIA (for arms 2 and 3):

Exclusion criteria will include the following:

• significant organ malfunction leading to clinical instability including liver disease, pulmonary disease, ischemic heart disease, heart failure, stroke, peripheral vascular disease, and anemia at investigator discretion
• other serious or chronic illness; history of serious or chronic illness; coronary artery disease, or peripheral vascular disease resulting in clinical instability
• pregnancy
• alcohol abuse, drug addiction or the use of illegal drugs
• positive HIV or hepatitis (B or C) screening tests (subjects will be notified of these test results).
• presence of other concomitant conditions which in the judgment of the investigators can influence vitamin C metabolism or vitamin C renal handling

For inpatient subjects, an additional exclusion criterion is consumption during the hospitalization of any foods or beverages other than those in the vitamin C free diet.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Irene T Rozga, R.N.; (301) 496-1069; irene.rozga@nih.gov

Contact: Ifechukwude C Ebenuwa, M.D.; (301) 435-6582; ifechukwude.ebenuwa@nih.gov

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00071526
• Other Study ID Numbers: 040021; 04-DK-0021
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ifechukwude C Ebenuwa, M.D.; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: May 15, 2024