Metabolic Effects of Betaine Supplementation
Study Details
Study Description
Brief Summary
Betaine is important in cellular metabolic pathways. Few epidemiologic studies link betaine levels to diabetes and cardiovascular disease. Small human studies suggest benefit for non-alcoholic liver disease. In this study we will determine if administration of betaine improves metabolic measures, liver fat and/or endothelial function in humans with glucose intolerance who are overweight.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
This study is a single site, prospective, randomized (1:1), double masked, placebo controlled trial to assess metabolic effects of betaine compared to placebo on glycemia and insulin sensitivity, liver fat and endothelial function.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Betaine
|
Drug: Betaine
Betaine or placebo administered orally in divided doses over 12 weeks
Other Names:
|
Placebo Comparator: Placebo
|
Drug: Placebo
Placebo administered orally in divided doses over 3 months
|
Outcome Measures
Primary Outcome Measures
- Fasting and 2 Hour Glucose Levels, Comparing Baseline and 12 Weeks. [baseline and 12 weeks]
Glucose levels were analyzed in the fasting state and two hours after glucose load, comparing baseline to 12 weeks.
- Change in Glucose AUC at 12 Weeks From Baseline (Glucose Tolerance) [baseline and 12 weeks]
Glucose tolerance was assessed by oral glucose tolerance, assessed using the change from baseline for fasting and 2 hour glucose, and change in Glucose AUC at 12 weeks from baseline was measured.
- Hepatic Fat, Change From Baseline [baseline and 12 weeks]
Intrahepatic triglyceride levels were assessed by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (Siemens 3T TIM Skyra, software version VD13; Siemens, Erlangen, Germany).
- Endothelial Function [baseline and 12 weeks]
Brachial artery reactivity to flow and nitroglycerin stimuli, assessed as percent change from baseline
- Insulin Sensitivity [Baseline and 12 weeks]
Euglycemic hyperinsulinemic clamp at baseline and at end of study (12 weeks) for assessment of: glucose disposal (M) at low (25 mU/m2/min) and high (180 mU/m2/min) insulin infusion rates, reported as raw data measurement of endogenous glucose production at basal and low insulin infusion (25 mU/m2/min), reported as change from measures at baseline of individual study days
Eligibility Criteria
Criteria
Inclusion Criteria:
-
- Men and women aged 21-65 years old;
-
- Dysglycemia/prediabetes is defined as impaired fasting glucose (≥100 mg/dl), impaired glucose tolerance (2 hour post 75 g oral glucose load 140-200 mg/dl) or HbA1c 5.7-6.5%);
-
- overweight to grade 3 obesity (BMI 25 to 45 kg/m2).
Exclusion Criteria:
-
- cystathionine beta-synthase (CBS deficiency);
-
- Presence of liver disease other than NAFLD;
-
- Use of medications causing steatosis;
-
- Known alcohol consumption ≥ 2 drink per day;
-
- Use of medications known to cause insulin resistance;
-
- Use of weight loss drugs (or program) within 3 months of screening;
-
- Treatment with any experimental drug within the past 6 months;
-
- Subjects must be willing to abstain from use of phosphodiesterase type 5 (PDE-5) inhibitors;
-
- Pregnancy or lactation, and women of child bearing potential must use adequate contraception;
-
- Surgery within 30 days of screening;
-
- Heart disease defined as New York Heart Association Class III or IV cardiac status or hospitalization for congestive heart failure, unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack or any revascularization within 6 months;
-
- Uncontrolled hypertension;
-
- eGFR <60; 14) History of acquired immune deficiency syndrome;
-
- History of malignancy within 5 years;
-
- Hemoglobin <12 g/dL (males), <10 g/dL (females);
-
- Triglycerides (TG) >500 mg/dL;
-
- Poor mental function or any other reason to expect patient difficulty in complying with study requirements;
-
- Metal clips or implants that preclude magnetic resonance imaging.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Joslin Diabetes Center and Brigham and Womens Hospital | Boston | Massachusetts | United States | 02215 |
Sponsors and Collaborators
- Joslin Diabetes Center
- American Diabetes Association
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- 2013P001265
- 7-13-CE-17
Study Results
Participant Flow
Recruitment Details | Study subjects with overweight and T2D risk factors were screened for dysglycemia and enrolled at 1 site in the US. |
---|---|
Pre-assignment Detail |
Arm/Group Title | Betaine | Placebo |
---|---|---|
Arm/Group Description | Betaine: Participants were instructed to take betaine 3300 mg (10 ml) orally twice daily for 10 days, then 4950 mg (15 ml) orally twice daily through 12 weeks. | Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks. |
Period Title: Overall Study | ||
STARTED | 15 | 13 |
Study Drug Initiated | 14 | 13 |
Completed Clamp | 13 | 12 |
Completed MRI | 13 | 12 |
Completed Endothelial Evaluation | 14 | 12 |
COMPLETED | 14 | 13 |
NOT COMPLETED | 1 | 0 |
Baseline Characteristics
Arm/Group Title | Betaine | Placebo | Total |
---|---|---|---|
Arm/Group Description | Betaine: Participants were instructed to take betaine 3300 mg (10 ml) orally twice daily for 10 days, then 4950 mg (15 ml) orally twice daily through 12 weeks. | Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks. | Total of all reporting groups |
Overall Participants | 14 | 13 | 27 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
61
(7)
|
57
(8)
|
59
(8)
|
Sex: Female, Male (Count of Participants) | |||
Female |
4
28.6%
|
4
30.8%
|
8
29.6%
|
Male |
10
71.4%
|
9
69.2%
|
19
70.4%
|
Race/Ethnicity, Customized (Count of Participants) | |||
Asian |
2
14.3%
|
0
0%
|
2
7.4%
|
Black or African American |
3
21.4%
|
2
15.4%
|
5
18.5%
|
White |
7
50%
|
11
84.6%
|
18
66.7%
|
Hispanic |
2
14.3%
|
0
0%
|
2
7.4%
|
Region of Enrollment (participants) [Number] | |||
United States |
14
100%
|
13
100%
|
27
100%
|
Outcome Measures
Title | Fasting and 2 Hour Glucose Levels, Comparing Baseline and 12 Weeks. |
---|---|
Description | Glucose levels were analyzed in the fasting state and two hours after glucose load, comparing baseline to 12 weeks. |
Time Frame | baseline and 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Betaine | Placebo |
---|---|---|
Arm/Group Description | Betaine: Participants were instructed to take betaine 3300 mg (10 ml) orally twice daily for 10 days, then 4950 mg (15 ml) orally twice daily through 12 weeks. | Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks. |
Measure Participants | 14 | 13 |
fasting glucose |
-5
|
3
|
2-hour glucose |
7
|
-4
|
Title | Change in Glucose AUC at 12 Weeks From Baseline (Glucose Tolerance) |
---|---|
Description | Glucose tolerance was assessed by oral glucose tolerance, assessed using the change from baseline for fasting and 2 hour glucose, and change in Glucose AUC at 12 weeks from baseline was measured. |
Time Frame | baseline and 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Betaine | Placebo |
---|---|---|
Arm/Group Description | Betaine: Participants were instructed to take betaine 3300 mg (10 ml) orally twice daily for 10 days, then 4950 mg (15 ml) orally twice daily through 12 weeks. | Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks. |
Measure Participants | 14 | 13 |
Mean (95% Confidence Interval) [mg*min/dL] |
340
|
-413
|
Title | Hepatic Fat, Change From Baseline |
---|---|
Description | Intrahepatic triglyceride levels were assessed by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (Siemens 3T TIM Skyra, software version VD13; Siemens, Erlangen, Germany). |
Time Frame | baseline and 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Betaine | Placebo |
---|---|---|
Arm/Group Description | Betaine: Participants were instructed to take betaine 3300 mg (10 ml) orally twice daily for 10 days, then 4950 mg (15 ml) orally twice daily through 12 weeks. | Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks. |
Measure Participants | 13 | 12 |
Mean (Standard Error) [percent change in hepatic triglyceride] |
-0.01
(0.02)
|
-0.03
(0.02)
|
Title | Endothelial Function |
---|---|
Description | Brachial artery reactivity to flow and nitroglycerin stimuli, assessed as percent change from baseline |
Time Frame | baseline and 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
One participant in the placebo group was not able to complete nitroglycerine-mediated dilation assessment. |
Arm/Group Title | Betaine | Placebo |
---|---|---|
Arm/Group Description | Betaine: Participants were instructed to take betaine 3300 mg (10 ml) orally twice daily for 10 days, then 4950 mg (15 ml) orally twice daily through 12 weeks. | Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks. |
Measure Participants | 14 | 13 |
Percent change in flow-mediated dilation |
-0.5
|
-1.9
|
Percent change in nitroglycerine-mediated dilation |
-0.9
|
-0.9
|
Title | Insulin Sensitivity |
---|---|
Description | Euglycemic hyperinsulinemic clamp at baseline and at end of study (12 weeks) for assessment of: glucose disposal (M) at low (25 mU/m2/min) and high (180 mU/m2/min) insulin infusion rates, reported as raw data measurement of endogenous glucose production at basal and low insulin infusion (25 mU/m2/min), reported as change from measures at baseline of individual study days |
Time Frame | Baseline and 12 weeks |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Betaine | Placebo |
---|---|---|
Arm/Group Description | Betaine: Participants were instructed to take betaine 3300 mg (10 ml) orally twice daily for 10 days, then 4950 mg (15 ml) orally twice daily through 12 weeks. | Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks. |
Measure Participants | 13 | 12 |
Glucose Utilization (M), 25 mU/m2/min, baseline |
90.4
(16.5)
|
62.8
(13.5)
|
Glucose Utilization (M), 25 mU/m2/min, 12 weeks |
110.9
(16.9)
|
73.5
(13.8)
|
Glucose Utilization (M), 180 mU/m2/min, baseline |
406.8
(30.4)
|
332.6
(39.1)
|
Glucose Utilization (M), 180 mU/m2/min, 12 weeks |
458.1
(38.7)
|
393.7
(44.1)
|
Endogenous Glucose Production, basal insulin |
.03
(.09)
|
-0.01
(0.09)
|
Endogenous Glucose Production, 25 mU/m2/min |
-0.01
(0.12)
|
-0.12
(0.13)
|
Adverse Events
Time Frame | Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug). | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Betaine | Placebo | ||
Arm/Group Description | Betaine: Participants were instructed to take betaine 3300 mg (10 ml) orally twice daily for 10 days, then 4950 mg (15 ml) orally twice daily through 12 weeks. | Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks. | ||
All Cause Mortality |
||||
Betaine | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/14 (0%) | 0/13 (0%) | ||
Serious Adverse Events |
||||
Betaine | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/14 (0%) | 0/13 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Betaine | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 4/14 (28.6%) | 6/13 (46.2%) | ||
Eye disorders | ||||
Irritation | 0/14 (0%) | 0 | 1/13 (7.7%) | 1 |
Gastrointestinal disorders | ||||
GI infection | 0/14 (0%) | 0 | 1/13 (7.7%) | 1 |
GI motility and defecation conditions | 1/14 (7.1%) | 1 | 0/13 (0%) | 0 |
Hepatobiliary disorders | ||||
Hepatic and hepatobiliary disorders | 1/14 (7.1%) | 1 | 0/13 (0%) | 0 |
Immune system disorders | ||||
Immune disorders | 0/14 (0%) | 0 | 1/13 (7.7%) | 1 |
Metabolism and nutrition disorders | ||||
Metabolism and nutrition | 1/14 (7.1%) | 1 | 0/13 (0%) | 0 |
Renal and urinary disorders | ||||
Renal impairment | 0/14 (0%) | 0 | 1/13 (7.7%) | 1 |
Urinary tract signs and symptoms | 0/14 (0%) | 0 | 1/13 (7.7%) | 2 |
Respiratory, thoracic and mediastinal disorders | ||||
Respiratory disorders NEC | 0/14 (0%) | 0 | 1/13 (7.7%) | 1 |
Respiratory tract infections | 1/14 (7.1%) | 1 | 0/13 (0%) | 0 |
Limitations/Caveats
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.
Results Point of Contact
Name/Title | Mary Elizabeth Patti MD |
---|---|
Organization | Joslin Diabetes Center |
Phone | 617 309 2635 |
mary.elizabeth.patti@joslin.harvard.edu |
- 2013P001265
- 7-13-CE-17