Trial Outcomes & Findings for Metabolic Effects of Betaine Supplementation (NCT NCT01950039)

NCT ID: NCT01950039

Last Updated: 2021-04-20

Results Overview

Glucose levels were analyzed in the fasting state and two hours after glucose load, comparing baseline to 12 weeks.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 28 participants
• Primary outcome timeframe: baseline and 12 weeks
• Results posted on: 2021-04-20

Participant Flow

Study subjects with overweight and T2D risk factors were screened for dysglycemia and enrolled at 1 site in the US.

Participant milestones

Measure	Betaine 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 Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks.
Overall Study STARTED	15	13
Overall Study Study Drug Initiated	14	13
Overall Study Completed Clamp	13	12
Overall Study Completed MRI	13	12
Overall Study Completed Endothelial Evaluation	14	12
Overall Study COMPLETED	14	13
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Metabolic Effects of Betaine Supplementation

Baseline characteristics by cohort

Measure	Betaine n=14 Participants 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 n=13 Participants Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks.	Total n=27 Participants Total of all reporting groups
Age, Continuous	61 years STANDARD_DEVIATION 7 • n=5 Participants	57 years STANDARD_DEVIATION 8 • n=7 Participants	59 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Race and Ethnicity · Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race and Ethnicity · Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race and Ethnicity · White	7 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized Race and Ethnicity · Hispanic	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	13 participants n=7 Participants	27 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and 12 weeks

Glucose levels were analyzed in the fasting state and two hours after glucose load, comparing baseline to 12 weeks.

Outcome measures

Measure	Betaine n=14 Participants 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 n=13 Participants Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks.
Fasting and 2 Hour Glucose Levels, Comparing Baseline and 12 Weeks. fasting glucose	-5 mg/dl Interval -12.0 to 1.0	3 mg/dl Interval -4.0 to 9.0
Fasting and 2 Hour Glucose Levels, Comparing Baseline and 12 Weeks. 2-hour glucose	7 mg/dl Interval -10.0 to 25.0	-4 mg/dl Interval -22.0 to 13.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Betaine n=14 Participants 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 n=13 Participants Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks.
Change in Glucose AUC at 12 Weeks From Baseline (Glucose Tolerance)	340 mg*min/dL Interval -993.0 to 1672.0	-413 mg*min/dL Interval -1749.0 to 923.0

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Betaine n=13 Participants 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 n=12 Participants Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks.
Hepatic Fat, Change From Baseline	-0.01 percent change in hepatic triglyceride Standard Error 0.02	-0.03 percent change in hepatic triglyceride Standard Error 0.02

PRIMARY outcome

Timeframe: baseline and 12 weeks

Population: One participant in the placebo group was not able to complete nitroglycerine-mediated dilation assessment.

Brachial artery reactivity to flow and nitroglycerin stimuli, assessed as percent change from baseline

Outcome measures

Measure	Betaine n=14 Participants 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 n=13 Participants Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks.
Endothelial Function Percent change in nitroglycerine-mediated dilation	-0.9 percent change from baseline Interval -4.0 to 2.1	-0.9 percent change from baseline Interval -4.1 to 2.4
Endothelial Function Percent change in flow-mediated dilation	-0.5 percent change from baseline Interval -3.3 to 2.3	-1.9 percent change from baseline Interval -4.7 to 1.0

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Euglycemic hyperinsulinemic clamp at baseline and at end of study (12 weeks) for assessment of:

1. glucose disposal (M) at low (25 mU/m2/min) and high (180 mU/m2/min) insulin infusion rates, reported as raw data

2. 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

Outcome measures

Measure	Betaine n=13 Participants 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 n=12 Participants Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks.
Insulin Sensitivity Glucose Utilization (M), 25 mU/m2/min, baseline	90.4 umol/kg/min Standard Error 16.5	62.8 umol/kg/min Standard Error 13.5
Insulin Sensitivity Glucose Utilization (M), 25 mU/m2/min, 12 weeks	110.9 umol/kg/min Standard Error 16.9	73.5 umol/kg/min Standard Error 13.8
Insulin Sensitivity Glucose Utilization (M), 180 mU/m2/min, baseline	406.8 umol/kg/min Standard Error 30.4	332.6 umol/kg/min Standard Error 39.1
Insulin Sensitivity Glucose Utilization (M), 180 mU/m2/min, 12 weeks	458.1 umol/kg/min Standard Error 38.7	393.7 umol/kg/min Standard Error 44.1
Insulin Sensitivity Endogenous Glucose Production, basal insulin	.03 umol/kg/min Standard Error .09	-0.01 umol/kg/min Standard Error 0.09
Insulin Sensitivity Endogenous Glucose Production, 25 mU/m2/min	-0.01 umol/kg/min Standard Error 0.12	-0.12 umol/kg/min Standard Error 0.13

Adverse Events

Betaine

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Betaine n=14 participants at risk 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 n=13 participants at risk Placebo: Participants were instructed to take identical amounts and appearance of placebo through 12 weeks.
Eye disorders Irritation	0.00% 0/14 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).	7.7% 1/13 • Number of events 1 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).
Gastrointestinal disorders GI infection	0.00% 0/14 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).	7.7% 1/13 • Number of events 1 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).
Gastrointestinal disorders GI motility and defecation conditions	7.1% 1/14 • Number of events 1 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).	0.00% 0/13 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).
Hepatobiliary disorders Hepatic and hepatobiliary disorders	7.1% 1/14 • Number of events 1 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).	0.00% 0/13 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).
Immune system disorders Immune disorders	0.00% 0/14 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).	7.7% 1/13 • Number of events 1 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).
Metabolism and nutrition disorders Metabolism and nutrition	7.1% 1/14 • Number of events 1 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).	0.00% 0/13 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).
Renal and urinary disorders Renal impairment	0.00% 0/14 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).	7.7% 1/13 • Number of events 1 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).
Renal and urinary disorders Urinary tract signs and symptoms	0.00% 0/14 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).	7.7% 1/13 • Number of events 2 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).
Respiratory, thoracic and mediastinal disorders Respiratory disorders NEC	0.00% 0/14 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).	7.7% 1/13 • Number of events 1 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).
Respiratory, thoracic and mediastinal disorders Respiratory tract infections	7.1% 1/14 • Number of events 1 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).	0.00% 0/13 • Adverse event data were collected for 14 weeks (during study drug administration and for 2 weeks after last study drug).

Additional Information

Mary Elizabeth Patti MD

Joslin Diabetes Center

Phone: 617 309 2635

Email: mary.elizabeth.patti@joslin.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place