Mark A. Levine, M.D.

Photo of Mark Levine
Scientific Focus Areas: Cancer Biology, Clinical Research, Molecular Biology and Biochemistry, Molecular Pharmacology

Clinical Trials

Open studies conducted by NIDDK Principal Investigators appear below. Study statuses may include the following:

  • Open: Recruiting - Currently recruiting participants and open to everyone who meets eligibility criteria.
  • Open: Active, Not Recruiting - Participants are receiving an intervention or being examined, however new participants are not being recruited or enrolled.
  • Open: Enrolling by Invitation - People in a particular population were selected in advance and invited to participate. The study is not open to everyone who meets the eligibility criteria.
  • Open: Available for Expanded Access - Patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.

Studies Seeking Patients

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

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.

The trial is Open with a status of Recruiting.

Investigator: Mark A Levine, M.D.

Referral Contacts: Email: Mark A Levine, M.D. Phone: (301) 402-5588

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Vitamin E Pharmacokinetics and Biomarkers in Normal and Obese Women

Background: - Vitamin E is an antioxidant that reduces the damaging effects of oxygen in the body. Most American men (90%) and women (96%) do not get enough vitamin E from their diets; however, the amount of vitamin E needed by the body has been studied only in men, not women. In addition, it is unknown whether another antioxidant, vitamin C, helps vitamin E in protecting the body. Because vitamin E is a fat-soluble vitamin, how much body fat a person has could affect the amount of vitamin E needed for protection. Objectives: This study has three arms to examine vitamin E requirements: - To determine the amount of fat required to get the best vitamin E absorption from a meal. - To determine the amount (i.e., best dose) of vitamin E that must be consumed before it can be measured in the blood. - To examine how vitamin E and vitamin C work together in the body, in conjunction with diet and vitamin supplements. Eligibility: - Arms 1 and 2: Women between the ages of 18 and 40 years who have a normal weight and body mass index (BMI) of 27 or less. - Arm 3: Women between the ages of 18 and 40 years who have a normal weight (BMI 27), who are overweight (BMI > 27), or who are overweight (BMI > 27) and have non insulin-dependent diabetes. Design: - Arm 1: Five studies, each lasting 1 month with 1 month off between studies (total study = 10 months). Participants will take 500 1,000 mg of vitamin C twice daily for 2 weeks before admission to the clinical center for 1 week. - Study 1: Participants will eat breakfast containing a known amount of fat, after which they will take a vitamin E pill as well as receive an IV injection of vitamin E. Other foods contain only negligible amounts of vitamin E. Blood and urine samples will measure levels of vitamin E and other substances. - Studies 2 5: Outpatient visits will consist of the same tests as in Study 1; however, the amount of fat in the breakfast will range from 0% to 40% in random order. During one of the studies, an adipose tissue biopsy will be collected to determine how much vitamin E is in the tissues. - Arm 2: Five studies, each lasting 1 month with 1 month off between studies (total study = 10 months). Preparation for Arm 2 is the same as in Arm 1. The proportion of fat, muscle, and water in the body will also be measured. - Study 1: Participants will eat breakfast containing 30% fat, after which they will take a vitamin E pill as well as receive an IV injection of vitamin E. Conditions and procedures are the same as in Arm 1. - Studies 2 5: Outpatient visits will consist of the same tests as in Study 1; however, the amount of vitamin E in the breakfast will range from 2 to 30 mg in random order. - Arm 3: Outpatient (2 to 6 weeks) and inpatient studies (4 to 6 weeks). - Outpatient study: Participants will take 500 1,000 mg of vitamin C daily and provide blood and urine samples, as well as an adipose tissue sample. - Inpatient studies: Two vitamin E inpatient studies. Before these begin, participants vitamin C blood levels will be reduced by means of a diet low in vitamin C. Blood tests will determine how quickly vitamin C leaves the body. Once the vitamin C level is reduced, the first vitamin E study will begin. Study A: The procedure for this study is the same as in Arm 2, Study 1. Study B: The procedure for this study is the same as in Study A, except that the participants blood vitamin C levels will be higher.

The trial is Open with a status of Recruiting.

Investigator: Mark A Levine, M.D.

Referral Contacts: Email: Sebastian J Padayatty, M.D. Phone: (301) 496-1069

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Urinary Vitamin C Loss in Diabetic Subjects

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.

The trial is Open with a status of Recruiting.

Investigator: Mark A Levine, M.D.

Referral Contacts: Email: Ifechukwude C Ebenuwa, M.D. Phone: (301) 435-6582

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Investigating the Use of Quercetin on Glucose Absorption in Obesity, and Obesity With Type 2 Diabetes

Quercetin is a compound naturally found in various foods. It may have some role in the treatment of obesity and diabetes. The purpose of this study is to investigate research volunteers with obesity or obesity with type 2 diabetes to determine whether quercetin affects the way glucose is absorbed by the body. Thirty two participants aged 19 to 65 who are considered to be medically obese or obese with type 2 diabetes will be enrolled in this study. Before the onset of treatment, they will undergo a medical history, physical exam, blood work, and urinalysis. During the study, participants will be given an oral glucose tolerance test three times; during these tests they will receive 1 or 2 grams of quercetin, or placebo. Researchers will collect blood samples and analyze the effect of the treatment on blood glucose.

The trial is Open with a status of Recruiting.

Investigator: Mark A Levine, M.D.

Referral Contacts: Email: Mark A Levine, M.D. Phone: (301) 402-5588

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The Body's Affect on Vitamin C

Pharmacokinetics is the term used for how the body affects a drug once it is taken. Vitamin C, also known as ascorbic acid, is an essential water soluble vitamin. Meaning, the body does not make Vitamin C it must be taken in through the diet. In this study researchers will attempt to determine how the amount of water consumed affects the level of vitamin C in the blood (specifically the plasma component of the blood). In this study researchers will take 13 subjects and place them on a Vitamin C restricted diet. Vitamin C levels will be measured twice a week on an outpatient basis until all subjects reach a desired low level of Vitamin C (12-15 micromolar plasma ascorbic acid concentration). Subjects will then be admitted and undergo 24 hour blood and urine collection. Following the collection of samples, subjects will then begin to receive Vitamin C orally (by mouth) and intravenously (injected into the vein). The dosage of Vitamin C will gradually increase from 30 mg-2500 mg divided into two daily doses. Blood and urine samples will be collected each time the dose is increased. The study will take approximately 18 weeks after which the subjects will be discharged in healthy condition.

The trial is Open with a status of Recruiting.

Investigator: Mark A Levine, M.D.

Referral Contacts: Email: Mark A Levine, M.D. Phone: (301) 402-5588

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