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Urinary Vitamin C Loss in Diabetic Subjects

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
ClinicalTrials.gov Identifier:
NCT00071526
First received: October 27, 2003
Last updated: February 24, 2015
Last verified: April 2014
  Purpose

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.


Condition
Diabetes Type 1
Diabetes Type 2
Healthy Volunteers

Study Type: Observational
Official Title: Urinary Vitamin C Loss in Subjects With and Without Diabetes

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 99999999
Study Start Date: October 2003
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

We propose to study an unlimited number of 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00071526

Contacts
Contact: Sebastian J Padayatty, M.D. (301) 496-1069 sebastianp@intra.niddk.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Sebastian J Padayatty, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )
ClinicalTrials.gov Identifier: NCT00071526     History of Changes
Other Study ID Numbers: 040021, 04-DK-0021
Study First Received: October 27, 2003
Last Updated: February 24, 2015
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Vitamin C
Diabetes Mellitus
Proteinuria
Renal Threshold
Healthy Volunteer

ClinicalTrials.gov processed this record on March 03, 2015