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Trial record 43 of 2097 for:    digestive | Open Studies | United States

Famine From Feast: Linking Vitamin C, Red Blood Cell Fragility, and Diabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 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:
NCT02107976
First received: April 5, 2014
Last updated: August 31, 2016
Last verified: July 2016
  Purpose

Diabetes type two is a debilitating disease that leads to chronic morbidity such as accelerated microvascular disease. Accelerated microvascular disease may produce blindness, end stage renal disease, myocardial infarction, stroke, and limb ischemia. Strategies to prevent or delay microvascular disease have the potential to improve the lives of millions and prevent catastrophic illness. The major focus of prevention of microvascular disease in diabetes has been on the endothelium and its role in protection of blood vessels. An unexpected means to prevent microvascular disease in diabetes may be coupled to the function of vitamin C in red blood cells (RBCs) of diabetic subjects. Based on new and emerging data, vitamin C concentrations in RBCs may be inversely related to glucose concentrations found in diabetes. Based on animal data, we hypothesize that RBCs with low vitamin C levels may have decreased deformability, leading to slower flow in capillaries and microvascular hypoxia, the hallmark of diabetic microangiopathy. Low vitamin C concentrations in RBCs of diabetic subjects may be able to be increased, by using vitamin C supplements. Findings in animals may not accurately reflect effects in humans because of species differences in mechanisms of vitamin C entry into RBCs. Therefore, clinical research is essential to characterize vitamin C physiology in RBCs of diabetic subjects. In this protocol we will investigate physiology of vitamin C in RBCs of diabetic subjects as a function of glycemia, with and without vitamin C supplementation. We will screen type II diabetic subjects on insulin and select those with low vitamin C levels and hemoglobin A1C concentrations of 8-12%. Selected subjects will be hospitalized twice, each time for approximately one week. As inpatients, subjects will have two venous sampling periods each of approximately 24 hours. For the first sampling period, controlled hyperglycemia will be induced by withdrawing insulin and providing a high carbohydrate load diet (70-75% carbohydrate). Hyperglycemia will not exceed 9 hours, and will be reversed by reinstituting insulin. The second sampling period, also for 24 hours, will be performed under conditions of euglycemic control.

During the two sampling periods, samples will be withdrawn via venous catheter for RBC deformability and vitamin C concentrations. At discharge, subjects will be placed on a vitamin C supplement and seen as outpatients at weekly intervals. After 3 or 6 weeks (depending on RBC vitamin C levels), subjects will be hospitalized again, and sampling repeated as described. In this manner, each subject serves as his/her own control, and deformability of red blood cells can be determined in relation to glycemia and to vitamin C concentrations in RBCs and plasma.


Condition Phase
Diabetes Type 2
Phase 1

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Famine From Feast: Linking Vitamin C, Red Blood Cell Fragility, and Diabetes

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Whether RBCs have low vitamin C concentrations in patients with poorly controlled diabetes, as measured by HBa1C [ Time Frame: ongoing ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: February 2014
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Detailed Description:

Diabetes type two is a debilitating disease that leads to chronic morbidity such as accelerated microvascular disease. Accelerated microvascular disease may produce blindness, end stage renal disease, myocardial infarction, stroke, and limb ischemia. Strategies to prevent or delay microvascular disease have the potential to improve the lives of millions and prevent catastrophic illness. The major focus of prevention of microvascular disease in diabetes has been on the endothelium and its role in protection of blood vessels. An unexpected means to prevent microvascular disease in diabetes may be coupled to the function of vitamin C in red blood cells (RBCs) of diabetic subjects. Based on new and emerging data, vitamin C concentrations in RBCs may be inversely related to glucose concentrations found in diabetes. Based on animal data, we hypothesize that RBCs with low vitamin C levels may have decreased deformability, leading to slower flow in capillaries and microvascular hypoxia, the hallmark of diabetic microangiopathy. Low vitamin C concentrations in RBCs of diabetic subjects may be able to be increased, by using vitamin C supplements. Findings in animals may not accurately reflect effects in humans because of species differences in mechanisms of vitamin C entry into RBCs. Therefore, clinical research is essential to characterize vitamin C physiology in RBCs of diabetic subjects. In this protocol we will investigate physiology of vitamin C in RBCs of diabetic subjects as a function of glycemia, with and without vitamin C supplementation. We will screen type II diabetic subjects on insulin and/or oral hypoglycemic medication(s) and select those with low vitamin C levels and hemoglobin A1C concentrations of 7-12%. Selected subjects will be hospitalized twice, each time for approximately one week. As inpatients, subjects will have two venous sampling periods each of approximately 24 hours. For the first sampling period, controlled hyperglycemia will be induced by withdrawing insulin and/or oral hypoglycemic medication(s) and providing a high carbohydrate load diet (70-75% carbohydrate). Hyperglycemia will not exceed 9 hours, and will be reversed by reinstituting insulin and/or oral hypoglycemic medication(s). The second sampling period, also for 24 hours, will be performed under conditions of euglycemic control.

During the two sampling periods, samples will be withdrawn via venous catheter for RBC deformability and vitamin C concentrations. At discharge, subjects will be placed on a vitamin C supplement and seen as outpatients at weekly intervals. After 3 or 6 weeks (depending on RBC vitamin C levels), subjects will be hospitalized again, and sampling repeated as described. In this manner, each subject serves as his/her own control, and deformability of red blood cells can be determined in relation to glycemia and to vitamin C concentrations in RBCs and plasma.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Male or female 18-60 years old, able to give informed consent.
  • Diabetes type 2 HgA1C 7-12 percent on insulin and/or oral hypoglycemic agents.
  • In general good health with no other significant illness.
  • Mild concomitant disease such as mild hypothyroidism (TSH <10) is acceptable.
  • Blood pressure with or without medication <160/90 mmHg with no known significant target organ damage (end organ damage includes the following: proliferative retinopathy, serum creatinine >1.5 or EGFR < 55 mL/min, symptomatic ischemic heart disease, severe congestive heart failure, advanced peripheral vascular disease.
  • Plasma/RBC vitamin C levels less than or equal to 30 microM.
  • Willingness to use effective contraceptive methods such as barrier method for the duration of study (female subjects).

EXCLUSION CRITERIA:

  • Diabetic type 1 subjects will be excluded due to the possibility of ketosis and hemodynamic instability with lack of insulin.
  • Any subjective or objective evidence of microangiopathy such as history of claudication, symptomatic peripheral vascular disease, symptomatic coronary artery disease, stroke, retinopathy, nephropathy (serum creatinine >1.5 or EGFR < 55 mL/min).
  • Subjects with retinopathy to avoid accelerated retinopathy with hyperglycemia.
  • Concomitant disease such as severe heart failure, severe liver disease (transaminases > 3 times normal), or severe systemic disease of any sort.
  • Participation in each protocol delineated evaluation procedure will be judged on a case by case basis with patient safety as the paramount consideration.
  • Pregnancy, breastfeeding.
  • History of diabetic ketoacidosis or hyperosmolar coma.
  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: NCT02107976

Contacts
Contact: Mark A Levine, M.D. (301) 402-5588 markl@mail.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
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Mark A Levine, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT02107976     History of Changes
Other Study ID Numbers: 140060  14-DK-0060 
Study First Received: April 5, 2014
Last Updated: August 31, 2016
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Diabetes
Red Blood Cells
Vitamin C
Plasma Vitamin C Levels

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vitamins
Ascorbic Acid
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on December 08, 2016