Treatment of Insulin Resistance in Hypertensive, Obese Adolescents
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), High Cholesterol, Endocrine |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology |
| Healthy: | No |
| Age Range: | 10 - 18 |
| Updated: | 4/2/2016 |
| Start Date: | October 2006 |
| End Date: | June 2007 |
| Contact: | Carolyn H Chi, MD |
| Email: | cchi@stanford.edu |
| Phone: | 650-723-5791 |
Randomized, Placebo Controlled, Double Blind Trial of Telmisartan in Hypertensive, Obese Adolescents
In this study, we propose using telmisartan, an angiotensin II receptor antagonist with
PPAR-gamma modulating activity, for a 12-week period to decrease blood pressure and insulin
levels in obese, hypertensive children. Telmisartan is currently approved for treatment of
adult hypertension. Recent adult studies, however, have shown telmisartan as an effective
medication for lowering insulin levels and improving insulin sensitivity. We will enroll 30
obese adolescents, ages 10 to 18 years, and randomly assign half of the group to receive
telmisartan and the other half to receive placebo (sugar-pill). We will obtain fasting
glucose and insulin levels, as well as other markers for insulin sensitivity and cholesterol
panel, at the beginning of the study, at each clinic visit in 4-week intervals, and at the
end of the study. We will obtain an imaging study (computed tomography, CT scan) on 10
randomly selected study patients (5 from each group) to examine the distribution of fat
tissue before and after treatment. Studies suggest that fat tissue in the subcutaneous
tissue is less harmful that fat tissues surrounding internal organs, such as the liver. We
will also provide nutritional handouts and exercise recommendations to each participant as a
life-style intervention. Each participant will be given a diary to record his or her diet
and exercise activities throughout the study.
PPAR-gamma modulating activity, for a 12-week period to decrease blood pressure and insulin
levels in obese, hypertensive children. Telmisartan is currently approved for treatment of
adult hypertension. Recent adult studies, however, have shown telmisartan as an effective
medication for lowering insulin levels and improving insulin sensitivity. We will enroll 30
obese adolescents, ages 10 to 18 years, and randomly assign half of the group to receive
telmisartan and the other half to receive placebo (sugar-pill). We will obtain fasting
glucose and insulin levels, as well as other markers for insulin sensitivity and cholesterol
panel, at the beginning of the study, at each clinic visit in 4-week intervals, and at the
end of the study. We will obtain an imaging study (computed tomography, CT scan) on 10
randomly selected study patients (5 from each group) to examine the distribution of fat
tissue before and after treatment. Studies suggest that fat tissue in the subcutaneous
tissue is less harmful that fat tissues surrounding internal organs, such as the liver. We
will also provide nutritional handouts and exercise recommendations to each participant as a
life-style intervention. Each participant will be given a diary to record his or her diet
and exercise activities throughout the study.
Hypothesis: This pilot study will provide data essential for designing a larger trial to
test the hypothesis that telmisartan treatment of obese children with insulin resistance and
hypertension will result in improved insulin levels and systolic blood pressure. Secondary
outcome measures will include the effects of telmisartan on total cholesterol, triglyceride,
HDL and LDL levels, body mass index (BMI), and body fat distribution.
Specific Aims for to Test Hypothesis:
Aim #1: Determine the change in insulin sensitivity in adolescents with obesity and
hyperinsulinemia before and after treatment with telmisartan. We hypothesize a significant
increase in insulin sensitivity following medical treatment. We will measure fasting insulin
and glucose levels for calculation of the homeostasis model assessment (HOMA) [29, 30].
Furthermore, we will calculate parameters of insulin production and insulin resistance from
simultaneous measurements of glucose, insulin, and C-peptide levels during an oral glucose
tolerance test (OGTT). We will check IGF BP-1 (insulin-like growth factor 1 binding protein)
level as an indirect measurement of insulin resistance. Due to the risks associated with
glucose clamps and continuous insulin infusion, we will not use this procedure in our study.
Aim #2: Determine the change in systolic blood pressure in adolescents with obesity and
hypertension before and after treatment with telmisartan. We hypothesize a significant
decrease in systolic blood pressure following medical treatment. Subjects will have blood
pressure checked at each clinic visit.
Aim #3: Evaluate changes in lipid profile and body mass index as secondary outcome measures
with telmisartan treatment. Subjects will have weight, height, and fasting lipid panel
checked at each clinic visit.
Aim #4: Characterize fat distribution before and after telmisartan treatment. A subset of
study participants will undergo magnetic resonance imaging (MRI) to characterize and
separate abdominal adipose tissue into its subcutaneous and visceral components. A one-slice
MRI will be obtained at 2 time-points during the study (weeks 0 and 12).
Aim #5: Determine the feasibility of using telmisartan for the treatment of hyperinsulinemia
and hypertension in obese adolescents. Study results will provide necessary data to
calculate the power needed for a multi-center, randomized, placebo-controlled trial of
telmisartan.
test the hypothesis that telmisartan treatment of obese children with insulin resistance and
hypertension will result in improved insulin levels and systolic blood pressure. Secondary
outcome measures will include the effects of telmisartan on total cholesterol, triglyceride,
HDL and LDL levels, body mass index (BMI), and body fat distribution.
Specific Aims for to Test Hypothesis:
Aim #1: Determine the change in insulin sensitivity in adolescents with obesity and
hyperinsulinemia before and after treatment with telmisartan. We hypothesize a significant
increase in insulin sensitivity following medical treatment. We will measure fasting insulin
and glucose levels for calculation of the homeostasis model assessment (HOMA) [29, 30].
Furthermore, we will calculate parameters of insulin production and insulin resistance from
simultaneous measurements of glucose, insulin, and C-peptide levels during an oral glucose
tolerance test (OGTT). We will check IGF BP-1 (insulin-like growth factor 1 binding protein)
level as an indirect measurement of insulin resistance. Due to the risks associated with
glucose clamps and continuous insulin infusion, we will not use this procedure in our study.
Aim #2: Determine the change in systolic blood pressure in adolescents with obesity and
hypertension before and after treatment with telmisartan. We hypothesize a significant
decrease in systolic blood pressure following medical treatment. Subjects will have blood
pressure checked at each clinic visit.
Aim #3: Evaluate changes in lipid profile and body mass index as secondary outcome measures
with telmisartan treatment. Subjects will have weight, height, and fasting lipid panel
checked at each clinic visit.
Aim #4: Characterize fat distribution before and after telmisartan treatment. A subset of
study participants will undergo magnetic resonance imaging (MRI) to characterize and
separate abdominal adipose tissue into its subcutaneous and visceral components. A one-slice
MRI will be obtained at 2 time-points during the study (weeks 0 and 12).
Aim #5: Determine the feasibility of using telmisartan for the treatment of hyperinsulinemia
and hypertension in obese adolescents. Study results will provide necessary data to
calculate the power needed for a multi-center, randomized, placebo-controlled trial of
telmisartan.
Inclusion Criteria:
Ages between 10.00 and 17.99 years
Body mass index (BMI) ≥ 95th percentile for age and gender using the CDC data
SBP ≥ 95th percentile for age, gender, and height using the fourth report from the
National High Blood Pressure Education Program (NHBPEP) guidelines.
Fasting plasma insulin concentration ≥ 20 U/mL will be required for study entry. This
insulin concentration is commonly used for defining insulin resistance.
Exclusion Criteria:
Subjects will be excluded from the study if they have known diabetes as defined by the
American Diabetes Association criteria, prior drug therapy to treat diabetes or insulin
resistance, recent glucocorticoid therapy within 3 months of the screening visit, current
drug therapy to treat hypertension, elevated creatinine (> 1.2mg/dL), elevated liver
enzymes (ALT > 80), history or current alcohol ingestion, existing pregnancy or high-risk
of becoming pregnant, other serious medical condition that the investigator determines may
put the subject at undue risk if enrolled in the study, or taking medications with
potential drug-drug interactions (anticoagulant, digoxin, diuretics).
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