Hypothalamic Obesity
Conditions
Keywords
Hypothalamic Obesity, Exenatide, Byetta, Craniopharyngioma
Brief summary
The primary aim of this study is to evaluate the effect of Exenatide on weight status (change in body mass index) of children treated for craniopharyngioma that have developed hypothalamic obesity at Children's Hospitals and Clinics of Minnesota. We hypothesize that Exenatide given to hypothalamic obese children for 6 months will reduce their body mass index significantly from baseline.
Detailed description
Hypothalamic obesity is when individuals suffer from acute weight gain after brain tumor treatment, involving secondary damage to the ventromedial nucleus of the hypothalamus, which may lead to obesity. The weight gain is uncontrolled and not receptive to diet and exercise interventions. The rate of long-term obesity in children diagnosed with craniopharyngioma can be as high as 50%. Exenatide, a drug indicated for diabetes, is an incretin mimicking agent that mimics the enhancement of glucose-dependent insulin secretion and several other antihyperglycemic actions of incretins has resulted in weight loss when given to diabetics. Exenatide shows potential to benefit patients suffering from hypothalamic obesity by slowing gastric emptying and therefore reducing food intake. Also increasing the glucagon-like peptide 1 (GLP-1) circulation, decreased due to obesity, at the already compromised GLP-1 receptor site of the hypothalamus could potentially help with regulation of appetite.
Interventions
DRUGExenatide
5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 20 weeks.
Sponsors
Amylin Pharmaceuticals, LLC.
Children's Hospitals and Clinics of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* \>/=6 months post surgical or radiation or chemotherapy treatment for 1° craniopharyngiomas or other suprasellar tumors * 10-21 years old * Age-and sex-adjusted BMI \>/=95% * Parent sign consent and patient sign assent
Exclusion criteria
* \< 6 months post surgical or radiation or chemotherapy treatment for 1° craniopharyngiomas or other suprasellar tumors * Pregnant or breastfeeding, or those women who plan to get pregnant * Renal impairment * Gastroparesis * Pancreatitis * Diabetes * \<1 month post initiation of Metformin treatment * Prescription or over-the-counter weight loss medications within 3 months of screening * Are actively participating in, or have participated in a formal weight loss program within the last 3 months * Have had bariatric surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BMI Change | 24 weeks | BMI was collected at baseline and 24 weeks |
| Waist to Height Ratio (WHtR) | 24 weeks | Waist circumference was measured at the natural waist level (midway between the lowest rib margin and the iliac crest) at baseline and 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Childhood Eating Behavior Questionnaire (CEBQ) | 24 weeks | The Child Eating Behaviour Questionnaire (CEBQ) was designed as parent-report measure comprised of 35 items, each rated on a five-point likert scale that ranges from never to always. We utilized the CEBQ as a self-report measure during this study; it has not been validated for such use. For the purposes of this study, we looked at the Satiety Responsiveness Subscale Scores (5 questions; total scores could range from 5-25 with lower scores denoting a lower level of satiety). The results reported show the change between baseline and week 24 scores. |
| Calorie Intake Based on 3-day Diet Records | 24 weeks | Dietary data were collected via 3-day diet records (Crawford et al. 1994) twice during the study, at baseline and week 24. Three-day diet records were collected on consecutive days including one weekend day. A registered dietitian (RD) instructed subjects on dietary data collection at baseline appointment. Depending on the age and capacity of the subject, the patient, parent or a collaboration of both recorded dietary intake. A RD entered dietary data into Nutritionist Pro software (First DataBank, SanBruno, CA) and the mean difference was analyzed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exenatide Exenatide: 5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 20 weeks. | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 2 |
Baseline characteristics
| Characteristic | Exenatide |
|---|---|
| Age, Categorical <=18 years | 16 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 15 years |
| BMI | 35 kg/m^2 |
| Child Eating Behaviour Questionnaire | 11.47 units on a scale |
| Height | 160.8 cm STANDARD_DEVIATION 14.3 |
| Hip Circumference | 113.5 cm STANDARD_DEVIATION 16 |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 11 Participants |
| Tumor Type Craniopharyngioma | 14 participants |
| Tumor Type Optic chiasm-hypothalamic glioma | 2 participants |
| Tumor Type Suprarasellar germinoma | 2 participants |
| Tumor Type Thalamic astrocytoma | 1 participants |
| Waist Circumference | 111.6 cm STANDARD_DEVIATION 19.5 |
| Waist to Height Ratio | 0.98 cm STANDARD_DEVIATION 0.08 |
| Weight | 89 kg STANDARD_DEVIATION 28.2 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 19 |
| serious Total, serious adverse events | 2 / 19 |
Outcome results
Primary
BMI Change
BMI was collected at baseline and 24 weeks
Time frame: 24 weeks
Population: The effects of exenatide on BMI were analyzed using a paired t-test comparing BMI at baseline with BMI after six months of treatment with each patient serving as his or her own control.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | BMI Change | -0.77 kg/m^2 |
p-value: 0.05t-test, 2 sided
Primary
Waist to Height Ratio (WHtR)
Waist circumference was measured at the natural waist level (midway between the lowest rib margin and the iliac crest) at baseline and 24 weeks
Time frame: 24 weeks
Population: All analyses were performed using SPSS (version 20.0.0, SPSS Inc, Chicago, IL).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Waist to Height Ratio (WHtR) | -2.06 percentage | Standard Deviation 0.08 |
p-value: 0.05t-test, 2 sided
Secondary
Calorie Intake Based on 3-day Diet Records
Dietary data were collected via 3-day diet records (Crawford et al. 1994) twice during the study, at baseline and week 24. Three-day diet records were collected on consecutive days including one weekend day. A registered dietitian (RD) instructed subjects on dietary data collection at baseline appointment. Depending on the age and capacity of the subject, the patient, parent or a collaboration of both recorded dietary intake. A RD entered dietary data into Nutritionist Pro software (First DataBank, SanBruno, CA) and the mean difference was analyzed.
Time frame: 24 weeks
Population: The sample size was small due to missing data
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | Calorie Intake Based on 3-day Diet Records | 406.700 kcals |
p-value: 0.05t-test, 2 sided
Secondary
Childhood Eating Behavior Questionnaire (CEBQ)
The Child Eating Behaviour Questionnaire (CEBQ) was designed as parent-report measure comprised of 35 items, each rated on a five-point likert scale that ranges from never to always. We utilized the CEBQ as a self-report measure during this study; it has not been validated for such use. For the purposes of this study, we looked at the Satiety Responsiveness Subscale Scores (5 questions; total scores could range from 5-25 with lower scores denoting a lower level of satiety). The results reported show the change between baseline and week 24 scores.
Time frame: 24 weeks
Population: Paired t-tests were performed to compare the satiety survey (continuous). Three subjects discontinued prior to completing the Week 24 CEBQ.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Exenatide | Childhood Eating Behavior Questionnaire (CEBQ) | 14 units on a scale |
p-value: 0.05t-test, 2 sided