Cardiovascular Disease, Impaired Glucose Tolerance, Insulin Resistance, Pediatric Obesity
Conditions
Keywords
Pediatric Obesity, Insulin Resistance, Glucose Tolerance, Adolescents, Acarbose, Continuous Glucose Monitoring (CGMS), Endothelial Dysfunction
Brief summary
The main purpose of this study is to determine whether treatment with acarbose attenuates post-prandial glycemic excursions in non-diabetic/pre-diabetic obese children as determined by continuous glucose monitoring systems (CGMS). To this effect the current pilot study involves a 6 week intervention with acarbose given to all subjects with either impaired glucose tolerance or an area under the curve of \>130 mg/dl during the screening oral glucose tolerance test. Three consecutive days of CGMS are then compared to before and during the intervention. The secondary objective addressed in this protocol is the collection of baseline measures of endothelial function in obese and lean children. Even though the duration of acarbose treatment may be too short to demonstrate a vascular effect, the pre and post intervention data would serve as preliminary data for anticipated future studies that assess the vascular effect of reduced post-prandial blood glucose levels.
Detailed description
We are particularly interested in examining whether acarbose lowered the percentage of glucose excursions ≥ 140 mg/dl in a real-life, home environment. At baseline, subjects underwent an oral glucose tolerance test (OGTT) and 72 hr of out-patient continuous glucose monitoring. They were treated with acarbose (50 mg with meals three times daily) for 6 weeks and repeat 72 hr CGMS profiles were obtained at the end of the study.
Interventions
DRUGAcarbose
At baseline, subjects underwent an OGTT and 72 hr of out-patient continuous glucose monitoring. They were treated with acarbose (50 mg with meals three times daily) for 6 weeks and repeat 72 hr CGMS profiles were obtained at the end of the study.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 25 Years
Healthy volunteers
Yes
Inclusion criteria
Obese Subjects: Inclusion Criteria: * Obesity (BMI \> 97%tile for age and sex matched normative data) * Good general health, taking no medication on a chronic basis * Age 12-19 yrs, in puberty (girls: breast: Tanner stage II to V, boys: testicular volume \>6ml) * Girls who are sexually active must use adequate birth control methods(such as barrier method or oral contraception) and must have a negative pregnancy test * Normal liver function tests
Exclusion criteria
* Raynaud's syndrome * Pregnancy or breastfeeding mothers * Smokers * Anemia (Hct \< 35) * Baseline creatinine \> 1.0 mg * Abnormal liver transaminases \> 1.5X the upper limit of normal * Presence of endocrinopathies (Cushing syndrome, hypothyroidism) * Presence or history of gastrointestinal disorders (Inflammatory bowl disease, irritable bowl disease, hernia, ileus) * Presence of significant chronic illness of any kind * Drug therapy (examples of commonly occurring drug therapy include any drugs to treat asthma, hypertension, dyslipidemia, insulin resistance, depression) * Psychiatric disorders * History of substance abuse (including anorexic agents) Control Subjects: Inclusion Criteria: * Lean (BMI \< 85%tile for age and sex matched normative data) * Good general health, taking no medication on a chronic basis * Age 12-25 yrs, in puberty (girls: breast: Tanner stage II to V, boys: testicular volume \>6ml) * Girls who are sexually active must use adequate birth control methods (such as barrier method or oral contraception) and must have a negative pregnancy test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Percentage of Glucose Values ≥ 140 mg/dl Over 72 Hours of Glucose Readings Measured With a Continuous Glucose Monitor | At baseline (before treatment) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acarbose Administration Acarbose : Subjects assigned to treatment will receive an exact supply of Acarbose to cover the initial 5 weeks of intervention. The medication will be distributed by the investigational pharmacy. Subjects will be instructed on the dosing schedule as follows (due to potential gastrointestinal side effects, the dose will be increased incrementally to desired levels).
Tablets (dose) of acarbose: Week 1 - 25 mg once a day (with dinner); Week 2 - 50 mg once a day (with dinner); Week 3 - 25 mg with breakfast and 50 mg with dinner; Week 4 - 50 mg with breakfast, 25 mg with lunch and 50 mg with dinner; Week 5-7 - 50 mg with breakfast, 50 mg with lunch and 50 mg with dinner. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not meet OGTT/ CGMS criteria | 5 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Acarbose Administration |
|---|---|
| Age Continuous | 15.2 years STANDARD_DEVIATION 1.1 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Mean Percentage of Glucose Values ≥ 140 mg/dl Over 72 Hours of Glucose Readings Measured With a Continuous Glucose Monitor
Time frame: At baseline (before treatment)
Population: The number of participants who completed the study were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acarbose Administration | Mean Percentage of Glucose Values ≥ 140 mg/dl Over 72 Hours of Glucose Readings Measured With a Continuous Glucose Monitor | 8 percentage of glucose excursions ≥ 140 | Standard Deviation 8 |
Primary
Mean Percentage of Glucose Values ≥ 140 mg/dl Over 72 Hours of Glucose Readings Measured With a Continuous Glucose Monitor
Time frame: After 6 Weeks (post treatment)
Population: The number of participants who completed the study were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acarbose Administration | Mean Percentage of Glucose Values ≥ 140 mg/dl Over 72 Hours of Glucose Readings Measured With a Continuous Glucose Monitor | 2 percentage of glucose excursions ≥ 140 | Standard Deviation 5 |