Effects of Exenatide on Hypothalamic Obesity

• Sponsor: Children's Hospitals and Clinics of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT01061775
• Collaborator: Amylin Pharmaceuticals, LLC. (Industry)
• Enrollment: 19
• Locations: 2
• Arm: 1
• Duration (Months): 110.4
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypothalamic Obesity	Drug: Exenatide	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Exenatide on Hypothalamic Obesity
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Mar 15, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exenatide 5mcg of exenatide will be given twice a day for 4 weeks and increased to 10 mcg twice a day for 20 weeks.	Drug: Exenatide; 5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 20 weeks.; Other Names: Byetta

Outcome Measures

Primary Outcome Measures

1. BMI Change [24 weeks]

   BMI was collected at baseline and 24 weeks

2. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Orange County	Orange	California	United States	92868
2	Children's Hospitals & Clincis of Minnesota	Saint Paul	Minnesota	United States	55102

Sponsors and Collaborators

• Children's Hospitals and Clinics of Minnesota
• Amylin Pharmaceuticals, LLC.

Investigators

• Principal Investigator: M. Jennifer Abuzzahab, MD, Children's Hospitals & Clinics of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Hospital website

Publications

None provided.

• Responsible Party: Children's Hospitals and Clinics of Minnesota
• ClinicalTrials.gov Identifier: NCT01061775
• Other Study ID Numbers: 0903-028
• First Posted: Feb 3, 2010
• Last Update Posted: Oct 8, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Children's Hospitals and Clinics of Minnesota: Hypothalamic Obesity; Exenatide; Byetta; Craniopharyngioma
• Additional relevant MeSH terms: Obesity; Exenatide

Study Results

Participant Flow

Arm/Group Title	Exenatide
Arm/Group Description	Participants received 5mcg of exenatide twice a day for 4 weeks and increased to 10 mcg twice a day for 20 weeks.
Period Title: Overall Study
STARTED	19
COMPLETED	16
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Exenatide
Arm/Group Description	Exenatide: 5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 20 weeks.
Overall Participants	19
Age (Count of Participants)
<=18 years	16 84.2%
Between 18 and 65 years	3 15.8%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	15
Sex: Female, Male (Count of Participants)
Female	8 42.1%
Male	11 57.9%
Region of Enrollment (participants) [Number]
United States	19 100%
Tumor Type (participants) [Number]
Craniopharyngioma	14 73.7%
Optic chiasm-hypothalamic glioma	2 10.5%
Suprarasellar germinoma	2 10.5%
Thalamic astrocytoma	1 5.3%
BMI (kg/m^2) [Mean (Full Range) ]
Mean (Full Range) [kg/m^2]	35
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	160.8 (14.3)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	89 (28.2)
Waist Circumference (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	111.6 (19.5)
Hip Circumference (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	113.5 (16)
Waist to Height Ratio (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	0.98 (0.08)
Child Eating Behaviour Questionnaire (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	11.47

Outcome Measures

1. Primary Outcome

Title	BMI Change
Description	BMI was collected at baseline and 24 weeks
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Exenatide
Arm/Group Description	Exenatide: 5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 20 weeks.
Measure Participants	16
Mean (95% Confidence Interval) [kg/m^2]	-0.77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.05
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Waist to Height Ratio (WHtR)
Description	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

Outcome Measure Data

Analysis Population Description

All analyses were performed using SPSS (version 20.0.0, SPSS Inc, Chicago, IL).

Arm/Group Title	Exenatide
Arm/Group Description	Exenatide: 5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 20 weeks.
Measure Participants	16
Mean (Standard Deviation) [percentage]	-2.06 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Childhood Eating Behavior Questionnaire (CEBQ)
Description	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

Outcome Measure Data

Analysis Population Description

Paired t-tests were performed to compare the satiety survey (continuous). Three subjects discontinued prior to completing the Week 24 CEBQ.

Arm/Group Title	Exenatide
Arm/Group Description	Exenatide: 5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 20 weeks.
Measure Participants	16
Mean (95% Confidence Interval) [units on a scale]	14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Calorie Intake Based on 3-day Diet Records
Description	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

Outcome Measure Data

Analysis Population Description

The sample size was small due to missing data

Arm/Group Title	Exenatide
Arm/Group Description	Exenatide: 5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 20 weeks. Of 55 potential participants screened, 19 agreed to participate. Reasons for decline included reluctance to add another medication to their current regimens, travel distance, and aversion to an injectable medication. Sixteen patients completed the study. Of the three who failed to complete the study, one was lost to follow up, and two dropped out due to difficulty adhering to the twice daily injections, but none experienced significant side effects from therapy. Three of the 19 patients were on chronic metformin therapy.
Measure Participants	10
Mean (95% Confidence Interval) [kcals]	406.700

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exenatide
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Arm/Group Title	Exenatide
Arm/Group Description	Exenatide: 5mcg twice a day for 4 weeks increased to 10 mcg twice a day for 20 weeks.
All Cause Mortality
	Exenatide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Exenatide
	Affected / at Risk (%)	# Events
Total	2/19 (10.5%)
Endocrine disorders
cholecystitis	2/19 (10.5%)	2
Other (Not Including Serious) Adverse Events
	Exenatide
	Affected / at Risk (%)	# Events
Total	17/19 (89.5%)
Gastrointestinal disorders
Nausea and stomachache	14/19 (73.7%)	20
vomiting	10/19 (52.6%)	20
Diarrhoea	3/19 (15.8%)	6
Abdominal Pain	4/19 (21.1%)	8
Blood in Stool	1/19 (5.3%)	2
Constipation	1/19 (5.3%)	1
Reflux Gastritis	1/19 (5.3%)	1
Absomen Sore to Touch	1/19 (5.3%)	1
General disorders
Pyrexia	1/19 (5.3%)	2
Fatigue	2/19 (10.5%)	2
Injection Site Pain	1/19 (5.3%)	1
Body Aches	2/19 (10.5%)	2
Immune system disorders
Seasonal Allergies	1/19 (5.3%)	1
Ear Infection	2/19 (10.5%)	4
Pharyngitis	2/19 (10.5%)	2
Sinusitis	1/19 (5.3%)	1
Infections and infestations
Nasopharyngitis	3/19 (15.8%)	3
Upper Respiratory Infection	1/19 (5.3%)	1
Investigations
Blood in Urine Present	1/19 (5.3%)	1
Metabolism and nutrition disorders
Decreased Appetite	2/19 (10.5%)	2
Musculoskeletal and connective tissue disorders
Back Pain	3/19 (15.8%)	3
Nervous system disorders
Headache	3/19 (15.8%)	3
Dizziness	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/19 (5.3%)	1
Rhinorrhoea	1/19 (5.3%)	1
Tonsillar Hypertrophy	1/19 (5.3%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/19 (5.3%)	1
Rash	1/19 (5.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.