Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02358928 |
| Other study ID # |
STU 082013 020 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 2014 |
| Est. completion date |
August 18, 2016 |
Study information
| Verified date |
January 2022 |
| Source |
University of Texas Southwestern Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Concurrent with the rising prevalence of childhood obesity, the co-morbid condition of
non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver
disease among children. NAFLD is characterized by accrual of excess triglycerides (TG) in the
liver that leads to inflammation, fibrosis, and cirrhosis. One-third of the pediatric
population has NAFLD, a disease strongly associated with insulin-resistance and
metabolic-syndrome (Met-S). NAFLD is predicted to become the leading cause of liver
transplantation in adults by 2030.
Current understanding of NAFLD indicates that presence of excess TG in liver is an absolute
requirement for disease progression. First-line therapy for NAFLD is focused on decreasing
adiposity and improving insulin sensitivity through diet and exercise. Recent adult data
indicate that dietary carbohydrate-restriction is more effective at reducing hepatic
TG-content than traditional calorie-restriction. Few studies have been conducted to establish
resolution of hepatic steatosis by any intervention. Such studies in pediatrics are primarily
limited by a need for liver biopsy. However, hepatic proton magnetic resonance spectroscopy
(H-MRS) is a new innovative tool used to quantitatively measure hepatic TG content in a
non-invasive manner.
The primary aim is to compare the impact of dietary weight loss via carbohydrate-restriction
and calorie-restriction on hepatic TG-content quantified by H-MRS in obese children with
biopsy-proven NAFLD and Met-S.
This IRB approved protocol is a randomized control study. The investigators will recruit
subjects from the Center for Obesity and its Consequences in Health and the pediatric
gastroenterology clinics between the ages of 11-17 years who meet criteria for NAFLD and
Met-S. A H-MRS will be obtained in each subject prior to the start of dietary intervention.
Fifty-four subjects will be randomized to either a carbohydrate-restricted or
calorie-restricted diet for 6 months with no change in baseline activity. A repeat H-MRS will
be compared to baseline to determine the whether dietary carbohydrate-restriction is superior
to calorie-restriction for reducing hepatic TG content. The investigators believe that
subjects on the carbohydrate-restricted diet will have marked decrease in hepatic TG content
compared to those in the calorie-restricted diet given the same degree of reduction in body
mass index.
Description:
Specific Aims and Hypothesis:
The Primary aim is:
To compare the impact of dietary weight loss via carbohydrate-restriction and
calorie-restriction on hepatic TG content quantified by H-MRS in obese children with
biopsy-proven NAFLD and Met-S.
Our Secondary aims are:
To compare BMI z-score, ALT (analine transaminase) and cytokeratin 18 in obese patients with
NAFLD and Met-S after a 6 month dietary weight loss via either carbohydrate or calorie
restriction.
Hypothesis: Obese children with biopsy-proven NAFLD and Met-S will experience a reduction in
liver TG content, assessed by H-MRS, concurrent with 6 months of dietary weight loss;
however, we anticipate that subjects undergoing carbohydrate restriction will experience a
greater reduction in hepatic fat than those undergoing calorie restriction due to the
limiting of precursors for lipid synthesis inherent to the diet (CHO) and the expected
increase in hepatic oxidative metabolism (TG accrual is attenuated while disposal is
enhanced).
Methodology:
Design:
Our study is a 6 month prospective randomized controlled trial with outcomes assessment
monthly for the first 6 months and a follow up visit at 10- 12 months after randomization.
Setting:
Recruitment and data collection will be completed at University of Texas Southwestern Medical
Center and Children's Health, Dallas TX by study personnel. All patients who agree to
participate will give informed written consent and assent. A study staff member will explain
the study and review the consent and HIPAA forms with each patient. A copy of each signed
form will be kept in the patient's study file. Each patient will also receive signed copies.
Subjects:
All patients referred (male and female) within the age range of 11 - 17 years who are obese
(BMI >= 95th percentile) and meet criteria for metabolic syndrome (MetS) and non-alcoholic
fatty liver disease (NAFLD) will be offered to participate in study.
Inclusion Criteria:
1. Age 11 - 17 years
2. Male and Female subjects
3. BMI >= 95th percentile according to CDC body mass index chart for age and gender
4. Must be willing to participate and undergo "willingness to change" evaluation
5. Metabolic Syndrome(MetS) which is defined when 3 of the following are met:
1. Central adiposity (waist circumference ≥90th% for age and sex)
2. Hypertriglyceridemia (triglycerides ≥ 110mg/dl)
3. Low HDL cholesterol ≤40mg/dl
4. Elevated blood pressure systolic or diastolic blood pressure > 90th % adjusted for
age, sex and height or ≥ 130/85
5. IFG (Impaired fasting glucose ≥ 100mg/dl or elevated HOMA- IR ≥3.16)
6. ALT greater than 60 U/L and Non Alcoholic Fatty Liver Disease based on histologic
confirmation on liver biopsy (minimum of 5% of hepatocytes with macrovesicular fat)
obtained within 6 months before randomization
Exclusion Criteria:
1. Those patients with a history of poor compliance or adherence to energy restriction
diets
2. Patients on medications that could alter appetite including glucocorticoids,
psychostimulants (Vyvanse, Adderall), psychotropic medications (Zoloft, Risperdal), and
antihyperglycemic medications (metformin, sulfonylurea)
3. Patients with the following illnesses:
1. Type 2 diabetes
2. Renal disease
3. Mental diseases (mood, psychotic and anxiety disorders)
4. Developmental delay
5. Autism and autism spectrum disorders
6. Any liver disease except for non alcoholic fatty liver (NAFLD)
7. Metabolic disorders (tyrosinemia, glycogen storage disease, lysosomal disorders)
8. Congenital heart disease
9. Myopathies or muscular disorders/disability
4. Patients who follow a (cultural or religious) vegetarian lifestyle as this would not be
compatible with Carbohydrate Restriction (need for high quality protein)
5. Prepubertal patients defined by a tanner stage of 1
6. Current or history of significant alcohol consumption
Concise Summary of Project:
This is a 6-month prospective, randomized control trial enrolling patients referred to the
Children's Medical Center COACH Program. The COACH Program is a medical weight management
clinic, which serves obese children in order to diagnose and treat associated co-morbid
conditions.
Subjects meeting all enrollment criteria will be randomized to either a carbohydrate- or
calorie-restricted diet. They will be committed to this fixed meal plan for 6 months and
dietary education by a certified dietician will be provided. This will include the allowed
caloric intake and content, which is calculated by a bioelectric impedance meter (GE In Body
520) specific to patient's age, gender, and weight.
The carbohydrate-restricted diet is composed of 20% carbohydrates, 35% protein and 45% fat.
The calorie-restricted diet is composed of 50%carbohydrate, 15-20% protein and 30-35% fat.
Patients will be seen by a psychologist to help with goal setting, self-monitoring and
problem solving. Dietary compliance will be followed regularly by weekly phone calls for the
first 3 months and then monthly afterwards by the research personnel. A 72-hour dietary
recall will be conducted by our dietician every other month. Subjects will be followed in the
COACH clinic monthly. A detailed schedule will be outlined and provided to the families at
each visit. Any missed appointments will be rescheduled within 3 to 7 days, and the families
will be contacted immediately to offer assistance for the next visit. During this study,
subjects will be monitored with urine tests and blood tests to ensure safety while undergoing
the prescribed diet.
The first proton hepatic magnetic spectroscopy (H-MRS) will be done prior to initiating the
dietary intervention. A second H-MRS will be obtained after 2 months (at visit 3) on the
assigned dietary therapy. The final H-MRS will be performed after completion of the 6 month
dietary intervention. At the 6 month completion, the subjects will be seen in clinic and
blood work with urine testing will be done. Their final visit will be 4 to 6 months post
dietary intervention to assess weight maintenance.
