The GRADE Study is a pragmatic, unmasked clinical trial that will compare commonly used
diabetes medications, when combined with metformin, on glycemia-lowering effectiveness and
The trial is Open with a status of Active, not recruiting.
- Researchers who study health and nutrition are interested in developing more accurate
methods of determining what people eat from day to day and how it affects their general
health. In particular, better methods are needed to determine if people are accurately
remembering what they ate. One possible method involves the use of biomarkers, or indicators
in urine, blood, saliva, fat, and hair, which are related to the intake of a particular food
in a consistent way. One set of biomarkers in blood samples and hair may be used to determine
the relative amount of meat, fish, and soda (corn/sugar cane) in a person s diet. However,
more research is needed to study the effectiveness of using these biomarkers to accurately
track dietary intake.
- To validate the use of biomarkers as representative of specific dietary intake patterns
- Healthy, nondiabetic men between 18 and 65 years of age.
- This study involves an initial screening visit and a 12-13 week inpatient dietary study
- Participants will be screened with a medical history and physical examination, as well
as blood and urine samples and a glucose tolerance test to exclude individuals who have
- After 3 days of a standard weight-maintaining diet, participants will have a glucose
tolerance test and a body fat scan; provide hair, blood, and fat tissue samples; and
complete questionnaires and performance tests.
- Participants will spend one day in a metabolic chamber to measure their energy
expenditure and general metabolism.
- Participants will then be randomized into one of eight carefully designed diets for 12
weeks. The diets will differ in the amount of meat, fish, and soda, including one diet
where none of the three biomarker-related foods will be permitted. Blood samples will be
collected throughout the study diet period.
- At the end of the 12-week study diet period, participants will provide additional hair,
blood, and fat tissue samples, and will have a second metabolism assessment in the
- One area in which obese and lean individuals may be different is how their bodies handle
water balance and thirst. Studies done in animals suggest that individuals with greater body
fat may tolerate periods without water better than lean animals. Other research has found a
link between the ability to tolerate periods without water and increased body weight.
Researchers are interested in studying whether the ability to tolerate periods without water
and ability to feel thirst might differ in lean versus obese individuals.
- To evaluate the effects of water deprivation and feelings of thirst in lean and obese
- Healthy individuals at least 18 years of age who are either lean (body mass index less than
26 kg/m(2)) or obese (body mass index at least 35 kg/m(2)).
- Participants will be screened with a medical history, physical examination, and blood
and urine tests.
- Participants will spend the entire study (13 days) as inpatients at the National
Institutes of Health Clinical Center.
- Participants will have the following tests and procedures:
- Body composition assessment (using low-level x-rays) to determine the percentage of fat
tissue in the body.
- Oral glucose tolerance test (similar to that often used to diagnose diabetes).
Individuals who are suspected to have diabetes will not be allowed to continue with the
- High salt infusion test, in which an infusion of saline (salt water) will be given for 2
hours and participants will respond to questions about how hungry and thirsty they feel
during the procedure.
- Water deprivation test, in which participants will go for 24 hours without water or food
and respond to questions about how hungry and thirsty they feel.
- 24-hour stay in a metabolic chamber to determine how many calories participants burn in
- A series of questionnaires about participants' eating habits, feelings about food, and
personal feelings, as well as computer-based tests involving the performance of various
- Measurement of free-living energy using doubly-labeled water, in which participants will
drink a sample of water with extra-heavy atoms of hydrogen and oxygen to evaluate the
amount of water in the body.
- 24-hour urine collection.
- Frequent blood samples, urine collection, and fat tissue biopsies during the various
- After the end of the 13-day study, participants will return after 1 week for a final
This study will determine whether electrical stimulation of an area of the brain called the
dorsolateral prefrontal cortex, which is important in determining the feeling of fullness
after eating, affects how much food a person eats and weight loss over 4 weeks. It will also
compare weight changes in people who attend weight loss counseling sessions and those who do
not over this period of time.
Obese, non-diabetic people between 18 and 60 years of age who are in good health and who live
in the Phoenix, AZ, metropolitan area are eligible for this study. Candidates must have a
body mass index of 35 kg/m(2) or more and weigh less than 350 pounds.
Participants are admitted to the NIH inpatient unit in Phoenix for the first 9 days of the
study for tests, which include meal tests to determine eating behaviors and caloric intake,
blood and urine tests, glucose tolerance test, weight measurement, psychological assessments
and DEXA scan to measure body fat. For 3 of the days, they will be asked to eat all of their
food from automated vending machines. Some subjects receive transcranial direct current
stimulation (TDCS). For this procedure, electrodes that conduct electricity are placed on the
head and arm and the current is turned on for 40 minutes. Some tingling may be felt under the
electrodes. Other subjects receive sham TDCS, with the current turned on only very briefly.
After the evaluations, subjects are discharged home from the NIH unit and instructed to eat
25 percent fewer calories than they consumed while on a weight maintenance diet the first 3
days of their inpatient stay. They maintain the lower calorie diet at home for 4 weeks.
During this period they come to the NIH unit 3 days a week to receive either real or sham
This study will investigate how to better predict why some individuals gain or lose weight
more easily than others. It will examine whether the increase in the amount of energy a body
burns in 24 hours with overeating or the decrease over 24 hours with fasting can help
determine how easily someone gains or loses weight.
Healthy people between 18 and 60 years of age who have a body mass index (BMI) between 18.5
kg/m(2) and 24 kg/m(2) (for overfeeding study) or a BMI greater than 27 kg/m(2) with a body
weight less than 350 pounds (weight loss study) may be eligible for this study. The study
requires a 10-week admission to the NIH Clinical Center (2-week baseline, 6-week
overfeeding/weight loss, 2-week post-weight change).
Participants undergo the following tests and procedures during the hospital admission:
- Medical history, physical examination and laboratory studies
- Questionnaires to assess eating behavior, food preferences, body composition, and
- Body composition assessment (height, weight, waist circumference, and fat mass and
muscle content through DXA and MRI scans)
- Oral glucose tolerance test
- Meal test to measure the response of certain hormones to food
- Activity monitors to determine activity level
- Metabolic chamber study to measure calories burned over 24 hours and monitor body
- Free-living energy use study to measure calories burned under normal home conditions
over 7 days
- Fat and muscle biopsies
- Dietary intervention: Measurements of food intake and energy loss over a 6-week
overfeeding (1.5 times the subject s normal food intake) or weight loss (one-half the
subject s normal food intake) program
Followup procedures after the inpatient stay:
- Height and weight measurements at 6 months (overfeeding study participants) and monthly
for the first year, at 3-month intervals for the second year, and then yearly for 3 more
years (weight loss study participants)
- Yearly visits (2-night inpatient stay) for all participants for repeat meal test, DXA,
oral glucose tolerance test, behavioral questionnaires and, in women who can become
pregnant, pregnancy test
This study, conducted at the NIH Clinical Research Unit at the Phoenix Indian Medical Center,
will examine how the body s metabolism (energy expenditure) changes when people overeat and
when they fast and how different diets (e.g., high-protein or high-fat) affect metabolism.
The results may provide information about whether there are mechanisms that make some people
more resistant than others to gaining weight when they eat more.
Non-smoking healthy subjects between 18 and 55 years of age who weigh no more than 350 pounds
may be eligible for this study. Participants undergo the following procedures:
- Pregnancy test for women of childbearing age.
- Oral glucose tolerance test. For this test, an I.V. line (needle attached to a plastic
tube) is inserted into a vein to allow several blood draws without repeated needle
sticks. After the first blood sample is drawn, the subject drinks a cola-flavored sugar
solution. Five additional blood samples are then drawn over 3 hours.
- Blood test for DNA (genetic) studies related to obesity, diabetes and related medical
- DEXA scan. This test measures body fat. The subject lies on a table while a very small
dose of X-rays is passed through the body.
- Respiratory chamber. This test measures how many calories the body burns a day and
assesses energy balance between intake and expenditure. Subjects stay in a room with two
windows, equipped with a sink, toilet, television and DVD player, desk, chair, telephone
and bed for 24 hours. The test is repeated five times during the first 18-day admission
and 3 times during the second 13-day admission. For the first two sessions, subjects are
fed a diet equal to the amount of energy their body uses. For the next 6 stays they are
fed double the amount of calories their body usually uses for 5 of the stays and fast
(consume nothing but water and soda without caffeine or calories) during 1 stay. The
overfeeding diets may be high or low in protein, normal in protein, or high in fat.
Blood tests are done on the day of each respiratory chamber session and a 24-hour urine
sample is collected for one day while in the chamber.
- Eating behavior questionnaires.
- Psychological performance tests.
Some participants are asked to volunteer to repeat two of the chamber studies to validate the
measurements. The repeat session includes only the fasting and the overfeeding with normal
All participants are followed at 6 months with blood tests, a DEXA scan, and urine tests
(including pregnancy test for women). At annual visits for years 1 through 7, participants
have the 6-month tests plus an oral glucose tolerance test.
The prevalence of obesity in the United States has reached alarming proportions with 33% of
adults over the age of 20 being overweight. Obesity is more than twice as prevalent, however,
in the Pima Indians of Arizona. Although there have been a number of advances in our
understanding of the genetics of obesity, the environmental influences on the genetic
expression of obesity requires further investigation.
In an effort to understand some of the influences on the high prevalence of obesity in the
Pima Indians, the present study was designed to investigate eating behaviors and food
preferences, most especially the preference for high fat foods, in sib-pairs of Pima Indians
who have been previously genotyped in our genomic scan for loci linked to diabetes/obesity.
Most specifically, we will utilize several questionnaires and methods of assessing eating
behavior and the preference for high fat foods to create a food intake phenotype. In
addition, we will study Caucasians so that comparisons can be made between these two groups.
We will make these evaluations by assessing eating behavior, food preferences including usual
fat intake and preferences for high fat foods, body image perceptions, and energy
expenditure. It is hoped that the data gathered from this study will elucidate some of the
risk factors for the development of obesity among the Pima Indians.