BetaFat: Beta Cell Restoration Through Fat Mitigation

• Sponsor: University of Southern California (Other)
• Overall Status: Completed
• CT.gov ID: NCT01763346
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 88
• Location: 1
• Arms: 2
• Duration (Months): 60
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Prediabetes; Type 2 Diabetes; Obesity	Drug: Metformin; Device: gastric banding	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Beta Cell Restoration Through Fat Mitigation
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Jun 1, 2018
• Actual Study Completion Date: Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: metformin subjects receiving metformin	Drug: Metformin; metformin 1000 mg bid
Experimental: gastric banding subjects receiving LAP-BAND	Device: gastric banding; LAP-BAND

Outcome Measures

Primary Outcome Measures

1. Steady State Beta Cell Compensation [24 months]

   mean plasma C-peptide concentration during clamp steady state, adjusted for mean clamp insulin sensitivity

Other Outcome Measures

1. Glycemia [24 months]

   fasting and 2-hour OGTT glucose levels

2. Glycemia [24 months]

   HbA1C

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

13. unable or unwilling to give informed consent

14. unable to adequately communicate with clinic staff

15. another household member is a participant or staff member

16. current or anticipated participation in another intervention research project that would interfere with any of the interventions/outcomes

17. likely to move away from participating clinic in next 2 years

18. current (or anticipated) pregnancy and lactation.

19. major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of the study

20. weight loss >5% in past three months for any reason except postpartum weight loss.

21. additional conditions may serve as criteria for exclusion at the discretion of the local site

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	91011

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 28, 2016
• Informed Consent Form - Apr 5, 2018

More Information

Publications

• RISE Consortium. Restoring Insulin Secretion (RISE): design of studies of β-cell preservation in prediabetes and early type 2 diabetes across the life span. Diabetes Care. 2014;37(3):780-8. doi: 10.2337/dc13-1879. Epub 2013 Nov 5.

• Responsible Party: Thomas Buchanan, Professor, University of Southern California
• ClinicalTrials.gov Identifier: NCT01763346
• Other Study ID Numbers: BETAFAT; U01DK094430; IIT - 000395
• First Posted: Jan 8, 2013
• Last Update Posted: Oct 21, 2019
• Last Verified: Sep 1, 2019

• Keywords provided by Thomas Buchanan, Professor, University of Southern California: type 2 diabetes; prediabetes; obesity; gastric banding; metformin
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Prediabetic State; Glucose Intolerance; Metformin

Study Results

Participant Flow

Recruitment Details	Recruited from Kaiser Permanente Southern California
Pre-assignment Detail	Five participants randomized to metformin and six participants randomized to gastric banding refused to initiate treatment

Arm/Group Title	Metformin	Gastric Banding
Arm/Group Description	subjects receiving metformin Metformin: metformin 1000 mg bid	subjects receiving LAP-BAND gastric banding: LAP-BAND
Period Title: Overall Study
STARTED	44	44
Received Intervention	39	38
COMPLETED	34	36
NOT COMPLETED	10	8

Baseline Characteristics

Arm/Group Title	Metformin	Gastric Banding	Total
Arm/Group Description	subjects receiving metformin Metformin: metformin 1000 mg bid	subjects receiving LAP-BAND gastric banding: LAP-BAND	Total of all reporting groups
Overall Participants	44	44	88
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	44 100%	44 100%	88 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	34 77.3%	35 79.5%	69 78.4%
Male	10 22.7%	9 20.5%	19 21.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	21 47.7%	19 43.2%	40 45.5%
Not Hispanic or Latino	23 52.3%	25 56.8%	48 54.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 9.1%	3 6.8%	7 8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	9 20.5%	7 15.9%	16 18.2%
White	31 70.5%	34 77.3%	65 73.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	44 100%	44 100%	88 100%
Hyperglycemic clamp (nmol/l adjusted for insulin sensitivity) [Geometric Mean (Inter-Quartile Range) ]
Geometric Mean (Inter-Quartile Range) [nmol/l adjusted for insulin sensitivity]	3.37	3.67	3.52
Oral Glucose Tolerance Test (mmol/l) [Mean (Standard Deviation) ]
fasting glucose	6.2 (0.8)	6.2 (0.7)	6.2 (0.75)
2-hour glucose	10.5 (2.6)	10.4 (2.7)	10.45 (2.65)
Body weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	96.1 (10.9)	97.5 (12.2)	96.8 (11.8)
Body Mass Index (kilograms per meters squared) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per meters squared]	35.0 (2.9)	35.7 (2.9)	35.53 (2.9)
Hemoglobin A1C (percent of hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent of hemoglobin]	5.82 (0.06)	5.92 (0.06)	5.87 (0.06)

Outcome Measures

1. Primary Outcome

Title	Steady State Beta Cell Compensation
Description	mean plasma C-peptide concentration during clamp steady state, adjusted for mean clamp insulin sensitivity
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Participants completing 24-month hyperglycemic clamp

Arm/Group Title	Metformin	Gastric Banding
Arm/Group Description	subjects receiving metformin Metformin: metformin 1000 mg bid	subjects receiving LAP-BAND gastric banding: LAP-BAND
Measure Participants	34	36
Geometric Mean (95% Confidence Interval) [(nmol/L) adjusted for M/I]	3.01	3.19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Metformin, Gastric Banding
	Comments	We selected a sample size that would allow detection of an effect size of ~0.6 or greater between gastric band and metformin groups for measures of β-cell function after two years, hypothesizing greater function in the gastric band group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	35 subjects per group provided 80% power to detect an effect size of 0.59, assuming a 2-sided p=0.05, adjustment for baseline measures using ANCOVA, and correlation of 0.5 between baseline and end-study measures.
	Method	General Linear Models
	Comments	Differences in primary outcomes between groups at 24-months were compared using general linear models with baseline values included as covariates.

2. Other Pre-specified Outcome

Title	Glycemia
Description	fasting and 2-hour OGTT glucose levels
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

participants completing 24 months of interventions

Arm/Group Title	Metformin	Gastric Banding
Arm/Group Description	subjects receiving metformin Metformin: metformin 1000 mg bid	subjects receiving LAP-BAND gastric banding: LAP-BAND
Measure Participants	34	36
fasting glucose	5.95 (0.11)	5.85 (0.18)
2-hour glucose	10.87 (0.57)	9.92 (0.54)

3. Other Pre-specified Outcome

Title	Glycemia
Description	HbA1C
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

participants completing 24 months of interventions

Arm/Group Title	Metformin	Gastric Banding
Arm/Group Description	subjects receiving metformin Metformin: metformin 1000 mg bid	subjects receiving LAP-BAND gastric banding: LAP-BAND
Measure Participants	34	36
Mean (Standard Error) [percent of hemoglobin]	5.84 (0.09)	5.73 (0.09)

Adverse Events

Time Frame	24 months
Arm/Group Title	Metformin		Gastric Banding
Arm/Group Description	subjects receiving metformin Metformin: metformin 1000 mg bid		subjects receiving LAP-BAND gastric banding: LAP-BAND
All Cause Mortality
	Metformin		Gastric Banding
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/38 (0%)
Serious Adverse Events
	Metformin		Gastric Banding
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/39 (5.1%)		4/38 (10.5%)
Gastrointestinal disorders
gastric band slippage requiring removal	0/39 (0%)	0	2/38 (5.3%)	2
acalcuous cholecystitis	0/39 (0%)	0	1/38 (2.6%)	1
Gastric sleeve surgery	1/39 (2.6%)	1	0/38 (0%)	0
Musculoskeletal and connective tissue disorders
Ankle fracture	1/39 (2.6%)	1	0/38 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
breast cancer	0/39 (0%)	0	2/38 (5.3%)	2
Other (Not Including Serious) Adverse Events
	Metformin		Gastric Banding
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/39 (46.2%)		3/38 (7.9%)
Gastrointestinal disorders
Port revision	0/39 (0%)	0	2/38 (5.3%)	2
dysphagia	0/39 (0%)	0	1/38 (2.6%)	1
stomach pain or discomfort	11/39 (28.2%)	11	0/38 (0%)	0
dairrhea	3/39 (7.7%)	3	0/38 (0%)	0
heartburn	1/39 (2.6%)	1	0/38 (0%)	0
nausea	1/39 (2.6%)	1	0/38 (0%)	0
General disorders
Lack of energy	1/39 (2.6%)	1	0/38 (0%)	0
Psychiatric disorders
Depression	1/39 (2.6%)	1	0/38 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.