| Conditions: |
|
Obesity - Weight Loss |
| Purpose: |
|
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
TDCS. Some subjects are also assigned to receive weight loss counseling sessions twice a
week, while others are not. At the end of the 4 weeks, subjects return to the NIH unit for a
5-day stay to undergo a repeat DEXA scan, meal tests, psychological assessment and blood
tests, and they will eat for another 3 days from the vending machines.
At the completion of the study, all participants may choose to receive 4 more weeks of TDCS
or behavioral weight loss counseling, or both.
|
| Study Summary: |
|
In our studies of brain function examining areas related to hunger and fullness, a part of
the brain called the left dorsolateral prefrontal cortex (DLPFC) was found to be less active
in obese versus lean individuals following a meal. Furthermore, in women who have lost and
maintained weight loss, the activity in this area following a meal is similar to that of
lean women, suggesting that the activity in this area may improve with weight loss. Two
recent studies have demonstrated a lack of increase in food craving following non-invasive
brain stimulation to the left DLPFC when compared to a sham control group that did not
receive brain stimulation.
The aim of our protocol is to investigate the effectiveness of one type of noninvasive brain
stimulation technique, transcranial direct current stimulation (TDCS) on food intake in
significantly overweight (BMI > 30 kg/m(2) individuals. In study 1, we will enroll
individuals who previously participated in this study and compare how anodal (active)
stimulation or sham (no stimulation) to the left DLPFC compares to their previous
stimulation condition in terms of both weight loss and food intake. The aim of Study 2 is
to compare active versus sham anodal LDLPFC stimulation in a new group of volunteers.
Study 2 will be a double-blind parallel study and volunteers will be randomized to receive
either active TDCS or no stimulation (sham) to the left DLPFC. During a 4-week outpatient
period, both groups will be asked to consume a diet that is a 25% reduction from their
calculated weight maintenance calories and come to the Unit 3x per week for stimulation
sessions. The primary outcome measurements will be total food intake during 3-d of ad
libitum intake from a computerized vending machine system, and weight loss during a 4-week
outpatient period. In study 1 we will also examine appetitive hormones and behavioral
factors, which might also mediate potential changes in food intake and weight loss following
TDCS to the left DLPFC. Positive findings from this study could demonstrate the utility of a
novel and safe treatment for severe obesity. Future studies could include longer clinical
trials of TDCS with extended follow-up durations.
|
| Criteria: |
|
- INCLUSION CRITERIA:
- BMI greater than or equal to 30 kg/m(2).
- Age 18-60 years. Women who are post-menopausal will be excluded from the study due to
changes in their metabolism that could affect weight loss. We will set the cutoff at
age 60 so that the age difference between the men and women is not too great for
analysis purposes. Minors under the age of 18 will be excluded because the time
requirements of the study are such that they would interfere with school schedules.
Additionally, while the risks of TDCS are minimal, there haven't been studies showing
how TDCS might affect the growing brain.
- Healthy, as determined by medical history, physical examination, and laboratory tests
- Right-handedness (because the treatment will be given to the left dorsolateral
prefrontal cortex and the evidence accumulated in this region was only in
right-handed individuals)
- Weight stable (plus or minus 5 percent) for last 3 months
EXCLUSION CRITERIA:
- Weight less than 350 lbs, as this is the weight limit of the DXA machine
- Type 2 diabetes (according to the World Health Organization diagnostic criteria)
- Endocrine disorders (Cushing's disease, pituitary disorders, and hypo- and
hyperthyroidism)
- Chronic pulmonary disorders, including chronic obstructive pulmonary disease that
would limit ability to follow the protocol (investigator judgment) and obstructive
sleep apnea syndrome; only subjects with mild or exercise-induced asthma on no
medications or on beta-adrenergic agonists only (such as albuterol) will be allowed
to enter the study (provided use of these agents is not required for 1 week before
study entry).
- Cardiovascular diseases (coronary heart disease, heart failure, arrhythmias, and
peripheral artery disease)
- Hypertension (blood pressure measurement higher than 140/90 mmHg on 2 or more
occasions or use of anti-hypertensive medications)
- Diagnosed gastrointestinal diseases, including inflammatory bowel diseases (e.g.
Crohn's disease and ulcerative colitis), malabsorption syndromes (e.g. celiac
disease), gastric ulcer (active); only subjects with gastro-esophageal reflux will be
allowed to enter the study
- Liver disease (cirrhosis, active hepatitis B or C, and AST or ALT greater than or
equal to 1.5 times normal)
- Renal disease (serum creatinine concentrations greater than or equal to 1.5 mg/dl
and/or overt proteinuria)
- Central nervous system disease (cerebrovascular accidents, dementia,
neurodegenerative disorders, epilepsy or history of head injury). Personal or
first-degree relative with a seizure history.
- Cancer requiring treatment in the past 5 years, except for non-melanoma skin cancers
or cancers that have clearly been cured or, in the opinion of the investigator, carry
an excellent prognosis (e.g., Stage 1 cervical cancer)
- Alcohol (more than 3 drinks per day) and/or drug abuse (such as amphetamines,
cocaine, heroin, or marijuana)
- Smoking more than 5 cigarettes per day
- Current psychiatric disorder, as diagnosed by the Structured Clinical Interview for
DSM-IV-R. Those who report suicidal ideation or clinically significant problems will
be immediately referred for appropriate treatment.
- Presence of metal in the cranial cavity
- Holes in the skull made by trauma or surgery
- Pregnancy or lactation. All women (who could bear children) not using a medically
approved method of contraception (surgical sterilization, intrauterine device, or a
combined method using at least 2 of the following: diaphragm, condom, spermicide)
will be excluded.
- Postmenopausal women or symptoms of perimenopause (e.g. hot flashes, onset of
irregular periods following age 40, elevation of FSH greater than 20 IU following age
40 years)
- Taking weight loss medications or psychotropic medication
- History of HIV infection or ongoing chronic infection (such as tuberculosis)
- Conditions not specifically mentioned above may serve as criteria for exclusion at
the discretion of the investigators
|
| NCT ID: |
|
NCT00739362 |
| Primary Contact: |
|
Principal Investigator
Marci Gluck, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Marci Gluck, Ph.D.
Phone: (602) 200-5312
Email: gmarci@mail.nih.gov
|
| Backup Contact: |
|
N/A |
| Location Contact: |
|
Phoenix, Arizona 85014
United States
Marci Gluck, Ph.D.
Phone: 602-200-5312
Email: gmarci@mail.nih.gov
Site Status: Recruiting |