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.
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, 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.