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Beta Cell Restoration Through Fat Mitigation (BetaFat)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by University of Southern California
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Thomas Buchanan, University of Southern California
ClinicalTrials.gov Identifier:
NCT01763346
First received: January 4, 2013
Last updated: February 9, 2015
Last verified: February 2015
History of Changes
  Purpose

Weight loss achieved through gastric banding will be superior to treatment with metformin in preserving or restoring pancreatic beta cell function in people with prediabetes or mild type 2 diabetes.


Condition Intervention
Prediabetes
Type 2 Diabetes
Obesity
 Drug: Metformin
Device: gastric banding

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Beta Cell Restoration Through Fat Mitigation

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Steady state beta cell compensation [ Time Frame: 0, 12, 24 months ] [ Designated as safety issue: No ]
    mean plasma C-peptide concentration during clamp steady state, adjusted for mean clamp insulin sensitivity

  • Maximum beta cell compensation [ Time Frame: 0, 12, 24 months ] [ Designated as safety issue: No ]
    area under plasma C-peptide curve 0-10 minutes after arginine bolus at hyperglycemia (~450 mg/dl), adjusted for insulin sensitivity


Secondary Outcome Measures:
  • Changes in body fat [ Time Frame: 0, 12, 24 months ] [ Designated as safety issue: No ]
    total and regional fat assessed by DEXA and MRI

  • Acute beta cell compensation [ Time Frame: 0, 12, 24 months ] [ Designated as safety issue: No ]
    incremental area under insulin and, separately, C-peptide curves during first ten minutes after glucose injection, adjusted for insulin sensitivity

  • Steady state and maximal insulin responses [ Time Frame: 0, 12, 24 months ] [ Designated as safety issue: No ]
    Mean plasma insulin concentration at clamp steady state; area under plasma insulin curve 0-10 minutes after arginine bolus at hyperglycemia (~450 mg/dl)

  • Insulin responses to oral glucose [ Time Frame: 0, 12, 24 months ] [ Designated as safety issue: No ]
    30-min insulin and C-peptide responses and modeled parameters of beta cell function from 3-hour frequently sampled oral glucose tolerance tests

  • Insulin sensitivity [ Time Frame: 0, 12, 24 months ] [ Designated as safety issue: No ]
    ratio of clamp steady state glucose utilization to clamp steady state plasma insulin level; Matsuda index, HOMA-S


Other Outcome Measures:
  • glycemia [ Time Frame: 0, 12, 24 months ] [ Designated as safety issue: No ]
    fasting and OGTT glucose levels, HbA1C

  • Blood and urine biomarkers [ Time Frame: 0, 6, 12, 18, 24 months ] [ Designated as safety issue: No ]
    adipokines, fatty acids
Estimated Enrollment: 88
Study Start Date: June 2013
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: metformin
subjects receiving metformin
 Drug: Metformin
metformin 1000 mg bid
Experimental: gastric banding
subjects receiving LAP-BAND
 Device: gastric banding
LAP-BAND

Detailed Description:

BetaFat is a 2-arm, unblinded study to compare gastric banding to treatment with metformin over a 24-month period in moderately obese adults with pre- or mild type 2 diabetes. The primary outcome will be change in β-cell compensation for insulin resistance, which the investigators will compare between groups. Secondary analyses will include other potential markers of β-cell health and potential mediators of treatment-specific effects. The main focus will be on mediators related to obesity. Clinically, the project will serve as a test of concept for use of gastric banding relatively early in the spectrum of obesity and β-cell disease. Biologically, the results will provide crucial information on potential mediators of β-cell failure and its arrest or reversal in the context of obesity. Those mediators will guide the development of more effective treatment and monitoring for the β-cell disease that causes type 2 diabetes.

  Eligibility
Ages Eligible for Study:   22 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Prior completion of at least two months in a diet, exercise and lifestyle intervention program within the past two years
  2. Fasting plasma glucose >90 mg/dl plus 2-hour glucose ≥140 mg/dl on 75 gm OGTT plus HbA1C ≤7.0%. There is no lower limit for the A1C and no upper limit for the OGTT 2-hour glucose based on prior studies that allow us to identify people with falling β-cell function
  3. Age 22-65 years
  4. Body mass index (BMI) 30-40 kg/m2
  5. For participants with diabetes, known duration <1 year
  6. No history of use of antidiabetic medications except during pregnancy

Exclusion Criteria:

  1. Contraindications to LapBand(see Appendix 1)
  2. Contraindication to MRI (claustrophobia; permanent metal objects such as pacemakers, prostheses, aneurysm clips)
  3. Underlying disease(s) likely to (a) limit life span to less than study duration and/or (b) increase risk of intervention outside of the study and/or (c) limit ability to participate in outcomes assessment and/or (d) limit participation
  4. An underlying disease known to have important effects on glucose metabolism
  5. Active infections
  6. Renal disease (serum creatinine ≥1.4 mg/dl for men; ≥1.3 mg/dl for women) or serum potassium abnormality (<3.4 or >5.5 mmol/l)
  7. Anemia (hemoglobin <11g/dl in women, <12 g/dl in men) or known coagulopathy
  8. Cardiovascular disease, including uncontrolled hypertension and symptomatic congestive heart failure. Participants must be able to safely tolerate administration of fluid/volume challenges during clamp studies.
  9. Serum AST >3 times upper limit of normal in local clinical lab
  10. Excessive alcohol intake
  11. Suboptimally treated thyroid disease

  12. Conditions or behaviors likely to affect the conduct of the study

    1. unable or unwilling to give informed consent
    2. unable to adequately communicate with clinic staff
    3. another household member is a participant or staff member
    4. current or anticipated participation in another intervention research project that would interfere with any of the interventions/outcomes
    5. likely to move away from participating clinic in next 2 years
    6. current (or anticipated) pregnancy and lactation.
    7. major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of the study
    8. weight loss >5% in past three months for any reason except postpartum weight loss.
  13. additional conditions may serve as criteria for exclusion at the discretion of the local site
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01763346

Contacts
Contact: Enrique Trigo trigo@usc.edu

Locations
United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 91011
Principal Investigator: Thomas A Buchanan, MD         
Sub-Investigator: Namir Katkhouda, MD         
Sub-Investigator: Elizabeth Beale, MD         
Sponsors and Collaborators
University of Southern California
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Thomas A Buchanan, MD University of Southern California
  More Information

No publications provided by University of Southern California

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Thomas Buchanan, Professor, University of Southern California
ClinicalTrials.gov Identifier: NCT01763346     History of Changes
Other Study ID Numbers: BETAFAT, U01DK094430, IIT - 000395
Study First Received: January 4, 2013
Last Updated: February 9, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Southern California:
type 2 diabetes
prediabetes
obesity
gastric banding
metformin

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
 Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 27, 2015