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A Cohort Study of Weight Loss and Gliosis

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ClinicalTrials.gov Identifier: NCT03578887
Recruitment Status : Recruiting
First Posted : July 6, 2018
Last Update Posted : July 12, 2019
Sponsor:
Information provided by (Responsible Party):
Ellen Schur, MD, MS, University of Washington

Tracking Information
First Submitted Date  ICMJE June 25, 2018
First Posted Date  ICMJE July 6, 2018
Last Update Posted Date July 12, 2019
Actual Study Start Date  ICMJE June 1, 2019
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2018)
  • Weight Loss [ Time Frame: During 6 Month Behavioral Weight Loss Program ]
  • Weight Regain [ Time Frame: During 12-Month Follow-Up After Intervention ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Cohort Study of Weight Loss and Gliosis
Official Title  ICMJE A Twin Study of Obesity Pathogenesis Using fMRI
Brief Summary Patients and clinicians need better options to prevent the weight regain that almost universally follows a weight loss intervention. In lay terms, a new, higher "set point" seems to occur after people gain weight. Evidence from some research studies reinforces these observations, showing that processes of energy homeostasis vigorously defend the higher level of adiposity for years, if not permanently. Only bariatric surgery appears to "re-set" to a lower level of adiposity. No clear mechanism has been elucidated to date that explains these phenomena. The current proposal endeavors to address this crucial scientific gap by translating preclinical data into human studies testing novel mechanistic hypotheses. Prior studies in rodents show that a high-fat diet causes inflammation and a cellular response, known as gliosis, within hypothalamic regions regulating energy balance and glucose homeostasis. Evidence further suggests that gliosis might play a pathogenic role in obesity and type 2 diabetes mellitus (T2D) because its development precedes weight gain and impaired glucose homeostasis and its inhibition improves metabolic health. Importantly, gliosis is detectable in mice and humans by magnetic resonance imaging (MRI). Using MRI, the investigators discovered the first evidence of gliosis in obese humans and went on to show associations of gliosis with insulin resistance in humans, independent of the level of adiposity. New findings suggest that people with T2D have more extensive gliosis than is seen in nondiabetic obese subjects. Further findings reveal that gliosis improves, but is not completely reversed, 8 mo. after Roux-en-Y gastric bypass (RYGB) surgery in T2D patients. It remains unknown whether gliosis improves similarly when weight loss occurs by lifestyle change or if the efficacy and durability of weight loss via bariatric surgery is partially explained by its ability to reverse gliosis via an as yet unknown mechanism of action. We therefore propose three studies in humans to discover 1) if hypothalamic gliosis is reversed by a standard behavioral weight loss intervention, 2) if the extent of gliosis predicts successful weight loss during, or weight regain after, behavioral weight loss, and 3) the time course of improvement in gliosis after RYGB and the relation of its improvement to the short- and long-term efficacy of RYGB. Future research would define dietary, environmental, or other risk factors for the development of hypothalamic gliosis in humans. Achieving a better understanding of the role of the brain in obesity and its treatment could open new avenues for research, intervention, and prevention.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Obesity, Gliosis, Weight-Loss
Intervention  ICMJE
  • Behavioral: Behavioral Weight Loss Program
    Behavioral Weight Loss Program is a modified version of the Diabetes Prevention Program (DPP).
  • Procedure: Roux-en-Y Gastric Bypass
    Subjects undergoing Roux-en-Y gastric bypass
Study Arms  ICMJE
  • Active Comparator: Lifestyle Cohort
    Participants Undergoing Behavioral Weight Loss Program
    Intervention: Behavioral: Behavioral Weight Loss Program
  • Active Comparator: Surgical Cohort
    Participants Scheduled for Roux-en-Y Gastric Bypass Surgery
    Intervention: Procedure: Roux-en-Y Gastric Bypass
  • No Intervention: Healthy Weight Control Cohort
    Healthy Weight Controls With No Intervention
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 25, 2018)
145
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2023
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Aged 25-64 years
  • Behavioral Weight Loss (BWL) & Roux-en-Y Gastric Bypass (RYGB): BMI 30- <56 kg/m²
  • RYGB: eligible for RYGB and not undergoing revision or reoperation
  • Healthy Weight Controls (HWC): BMI 18.5-24.9 kg/m²

Exclusion Criteria:

  • T2D in BWL or HWC
  • Poorly controlled hypertension or coronary artery disease, or chronic disease (e.g. cancer, multiple sclerosis, autoimmune disease, rheumatic disease) Blood Pressure ( > 160/100 mmHG) Heart Rate ( > 110 bpm)
  • Chronic kidney disease (GFR <60 mL/min/1.73 m²)
  • A1c > 8.5% in RYGB; A1c ≥ 6.5% for BWL and HWC groups,
  • Current use of insulin, GLP-1 agonists, DPP-4 inhibitors, thiazolidinediones or medications known to alter metabolic function (e.g. atypical antipsychotics, corticosteroids),
  • Pregnancy or breastfeeding
  • MRI contraindications (e.g. implanted metal, claustrophobia), or unable to have MRI or fit in MRI scanner
  • Current smoking/daily use of nicotine containing products (cigarettes, e-cigarettes, vaping or other nicotine containing products) or heavy alcohol use
  • Weight >450 pounds (iDXA limit)
  • T2D (for BWL or HWC),
  • Weight-reduced from lifetime maximum weight by > 15%
  • Weight not stable over past 3 mos. (± 10%)
  • History of eating disorder or current eating disorder, currently enrolled in a weight loss program or taking medications to lose weight
  • Severe food allergies
  • Inability to participate in a weight loss program (BWL)
  • Any condition that the study physician determines to be unsafe for participation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Roz De Leon 206-616-6360 uwwebs@uw.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03578887
Other Study ID Numbers  ICMJE STUDY00002978
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ellen Schur, MD, MS, University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ellen Schur, MD, MS University of Washington
PRS Account University of Washington
Verification Date July 2019

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