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Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

14-DK-0060

Sponsoring Institute

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 65

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Diabetes;
Red Blood Cells;
Vitamin C;
Plasma Vitamin C Levels

Recruitment Keyword(s)

None

Condition(s)

Diabetes Type 2

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Institute of Diabetes and Digestive and Kidney Diseases

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.

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Eligibility

INCLUSION CRITERIA:

Arm 1

-Male or female 18-65 years old, able to give informed consent.

-Diabetes type 2 HgA1C less than or equal to 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.

-Willingness to use effective contraceptive methods such as barrier method for the duration of study (female subjects).

Arm 2

Above criteria with addition of RBC vitamin C concentration greater than micrM prior to inpatient studies.

EXCLUSION CRITERIA (Arm ! and 2):

-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.

-Subjects with clear evidence of non-compliance with protocol/study instructions.


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Citations:

Ali SM, Chakraborty SK. Role of plasma ascorbate in diabetic microangiopathy. Bangladesh Med Res Counc Bull. 1989 Dec;15(2):47-59.

Baskurt OK, Hardeman MR, Uyuklu M, Ulker P, Cengiz M, Nemeth N, Shin S, Alexy T, Meiselman HJ. Comparison of three commercially available ektacytometers with different shearing geometries. Biorheology. 2009;46(3):251-64. doi: 10.3233/BIR-2009-0536.

Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA. 2002 May 15;287(19):2570-81.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Ifechukwude C. Ebenuwa, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
BG 10 RM 4D51
10 CENTER DR
BETHESDA MD 20814
(301) 435-6582
ifechukwude.ebenuwa@nih.gov

Irene T. Rozga, R.N.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health
Building 10
Room 6C432B
10 Center Drive
Bethesda, Maryland 20892
(301) 496-1069
irene.rozga@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT02107976

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