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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02107976
Recruitment Status : Recruiting
First Posted : April 9, 2014
Last Update Posted : September 10, 2020
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )

Brief Summary:

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 or disease
Diabetes Type 2

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Famine From Feast: Linking Vitamin C, Red Blood Cell Fragility, and Diabetes
Study Start Date : April 5, 2014
Estimated Primary Completion Date : February 29, 2024
Estimated Study Completion Date : February 29, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin C

Type II diabetics

Primary Outcome Measures :
  1. Whether RBCs have low vitamin C concentrations in patients with poorly controlled diabetes, as measured by HBa1C [ Time Frame: End of study ]
    changes in RBC vitamin C levels in diabetics in relation to acute glycemic control

Secondary Outcome Measures :
  1. RBC deformability [ Time Frame: end of study ]
    effect of vitamin C supplementation on RBC deformability

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
primary clinical, type II diabetic subjects who have participated in 04-DK-0021 will be invited to participate in the study

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.


  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02107976

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Contact: Irene T Rozga, R.N. (301) 496-1069
Contact: Ifechukwude C Ebenuwa, M.D. (301) 435-6582

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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 Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Ifechukwude C Ebenuwa, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Additional Information:
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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Identifier: NCT02107976    
Other Study ID Numbers: 140060
First Posted: April 9, 2014    Key Record Dates
Last Update Posted: September 10, 2020
Last Verified: September 2, 2020
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ):
Red Blood Cells
Vitamin C
Plasma Vitamin C Levels
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases