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Trial record 4 of 6 for:    "Hypothalamic Obesity" | "Hormones"

Energy Balance & Weight Loss in Craniopharyngioma-related or Other Hypothalamic Tumors in Hypothalamic Obesity (ECHO)

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ClinicalTrials.gov Identifier: NCT02664441
Recruitment Status : Active, not recruiting
First Posted : January 27, 2016
Last Update Posted : April 4, 2019
Sponsor:
Collaborators:
Children's Hospitals and Clinics of Minnesota
Vanderbilt University
Information provided by (Responsible Party):
Christian Roth, Seattle Children's Hospital

Tracking Information
First Submitted Date  ICMJE January 4, 2016
First Posted Date  ICMJE January 27, 2016
Last Update Posted Date April 4, 2019
Study Start Date  ICMJE March 2016
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2016)
Percent change of body mass index (BMI) as calculated by the formula: body weight in kg divided by height in meters². [ Time Frame: Baseline and 36 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02664441 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2016)
  • Changes in in body composition as assessed by body fat mass using dual energy x-ray absorptiometry (DEXA) [ Time Frame: Baseline and 36 weeks ]
  • Changes in fat and total calorie intake assessed by free buffet meal analysis. [ Time Frame: Baseline and 36 weeks ]
  • Changes in fasting glucose [ Time Frame: Baseline and 36 weeks ]
  • Changes in HDL cholesterol and triglycerides assessed by fasting lipids [ Time Frame: Baseline and 36 weeks ]
  • Changes in inflammation assessed by high sensitive cardio-reactive protein (hsCRP) [ Time Frame: Baseline and 36 weeks ]
  • Changes of insulin resistance assessed by fasting insulin used for homeostasis model assessment of insulin resistance (HOMA-IR) using the formula insulin [mU/l] x glucose [mmol/l]) / 22.5 [ Time Frame: Baseline and 36 weeks ]
  • Changes of circulating leptin levels [ Time Frame: Baseline and 36 weeks ]
  • Changes of energy expenditure assessed by doubly labeled water analysis [ Time Frame: Baseline and 36 weeks ]
  • Changes of energy intake assessed by Automated Self-Administered 24-Hour Dietary Recall (ASA24-Kids) [ Time Frame: Baseline and 36 weeks ]
  • Changes in glucose 120 minutes following an oral glucose tolerance test [ Time Frame: Baseline and 36 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Energy Balance & Weight Loss in Craniopharyngioma-related or Other Hypothalamic Tumors in Hypothalamic Obesity
Official Title  ICMJE Glucagon-Like Peptide-1 Agonist Effects on Energy Balance in Hypothalamic Obesity
Brief Summary The proposed multicenter study will test the effect of glucagon-like peptide (GLP)-1 agonist exenatide once weekly extended-release (ExQW, Bydureon®) on clinical outcomes and metabolic parameters in a double-blind, placebo-controlled 36 week randomized trial with an 18 week open label extension. Following baseline testing, 48 patients will be randomly assigned with equal allocation to ExQW or matching placebo injection for 36 weeks, followed by an 18 week open label extension during which all patients receive ExQW. Changes of weight status, body composition, free-living total daily energy expenditure (EE) by doubly labeled water (DLW), activity by acetimetry, energy intake (questionnaires and food diary), as well as glucose tolerance and hormonal parameters of energy homeostasis and insulin resistance will be assessed before treatment and at the end of the placebo-controlled phase (week 36). Activity, metabolic outcomes, energy intake will be also assessed at study week 18 (mid treatment of randomized study), as well as week 54 (end of open label treatment).
Detailed Description

Excessive weight gain and its cardiometabolic sequela are frequent complications of hypothalamic tumors, a condition known as hypothalamic obesity (HO). Most tumors in this region are craniopharyngiomas (CP),1 which constitute 5-9% of childhood brain tumors. Patients with CP typically become obese and have more features of the metabolic syndrome compared to matched controls. Overall, a 3-19-fold higher cardiovascular mortality had been reported, and a recent nationwide population-based study in Sweden demonstrated increased rates for cerebral infarction (7-fold), death due to cerebrovascular diseases (5-fold), and type 2 diabetes mellitus (6-fold) in CP patients in comparison to the general population. Thus, early and effective management of obesity is vital for this population, which is more resistant to treatment than uncomplicated obesity. Recognized risk factors for severe obesity include large hypothalamic tumors or lesions affecting several medial and posterior hypothalamic nuclei that impact satiety signaling pathways. Structural damage in these nuclei often lead to uncontrolled appetite, rapid weight gain, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure (EE), and increased energy storage in adipose tissue. Recently, the investigators developed a semi-quantitative assessment of hypothalamic damage on brain magnetic resonance imaging (MRI) to predict the risk for HO development in CP.

Previous results of treating HO with a glucagon-like-peptide-1 receptor agonist (GLP1RA) in rats and humans provide promising proof-of-principle data to support this current randomized clinical trial. The primary hypothesis of this study is that drugs causing weight loss via intact hindbrain signaling pathways offer a desperately needed option for treatment of HO, even in very obese HO subjects with severe hypothalamic damage. Induction of weight loss by GLP1RAs is believed to be related to multiple mechanisms involving the gastrointestinal tract, vagus nerve, and the brain leading to increased satiety. Peripheral administration of GLP-1 or GLP1RA reduces blood glucose and energy intake in humans and rodents, and long-term treatment results in loss of body weight. Critically, the investigators do not know whether GLP1RA treatment affects EE and activity, or whether the site and size of brain lesions affect responses to GLP1RA treatment.

The investigators' previous clinical studies of the GLP1RA exenatide in obese adolescents and adults have generated the critical safety and efficacy data needed to design a clinical trial. In a pilot study conducted at Children's Hospitals and Clinics of MN, pretreatment hyperphagia was associated with BMI reduction. Using these data, the investigators have designed a prospective, multicenter trial that will examine the effects of GLP1RA on BMI, cardiovascular disease (CVD) risk factors, energy homeostasis and other factors in subjects with HO secondary to CP.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hypothalamic Obesity
Intervention  ICMJE
  • Drug: Exenatide
    Weekly injections of active drug.
    Other Name: Bydureon®
  • Drug: placebo
    Weekly placebo injections
Study Arms  ICMJE
  • Active Comparator: Exenatide once weekly extended-release
    Injections of glucagon-like peptide (GLP)-1 agonist exenatide once weekly extended-release (Bydureon®) for 36 weeks in randomized intervention followed by 18 weeks open label exenatide once weekly extended-release.
    Intervention: Drug: Exenatide
  • Placebo Comparator: Matching placebo
    Weekly injections of placebo for 36 weeks followed by 18 weeks open label exenatide once weekly extended-release.
    Intervention: Drug: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 22, 2016)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 10-25 years at time of enrollment
  • Diagnosis of hypothalamic obesity with age- and sex adjusted BMI ≥ 95% or BMI ≥30 kg/m² if over 18 y
  • History of craniopharyngioma or another tumor located in the hypothalamic area
  • Hypothalamic lesion documented by neuroradiology
  • ≥ 6 months post-surgical or radiation treatment
  • Weight stable or increasing over 3 months prior to screening visit
  • Stable hormone replacement for at least 3 months prior to screening visit

Exclusion Criteria:

  • Renal impairment (GFR<60 ml/min/1.73m² using the Schwarz formula)
  • History of gastroparesis; pancreatitis or gallstones (unless status post cholecystectomy)
  • Family history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma metabolic disorders
  • Any insulin-treated diabetes mellitus, poorly controlled type 2 diabetes (HbA1c ≥ 10%), or any other chronic serious medical conditions such as cardiovascular disease, malignancy or hematologic disorder, complicated syndromic disorder, or psychiatric disorders (schizophrenia, major depression, history of suicide attempts)
  • Calcitonin >50 mg/L at screening
  • Initiation of weight loss medications within 3 months of screening visit
  • Previous donation of blood >10% of estimated blood volume within 3 months prior study
  • Current warfarin use
  • Current use of any other GLP1 receptor agonist
  • Untreated thyroid disorder or adrenal insufficiency
  • History of bariatric surgery or planned bariatric surgery until end of study
  • Pregnancy, lactation or expectation to conceive during study period
  • Subject unlikely to adhere to study procedures in opinion of investigator
  • Subject with contraindication to neuroimaging by MRI
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02664441
Other Study ID Numbers  ICMJE R01DK104936-01A1( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Christian Roth, Seattle Children's Hospital
Study Sponsor  ICMJE Seattle Children's Hospital
Collaborators  ICMJE
  • Children's Hospitals and Clinics of Minnesota
  • Vanderbilt University
Investigators  ICMJE
Principal Investigator: Christian Roth, MD Seattle Childrens
PRS Account Seattle Children's Hospital
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP