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Metabolic Effects of Betaine Supplementation

Primary Purpose

Obesity, Dysglycemia

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Betaine

Placebo

About this trial

This is an interventional other trial for Obesity focused on measuring Obesity, Glucose Intolerance

Eligibility Criteria

21 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

1) Men and women aged 21-65 years old;
2) 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%);
3) overweight to grade 3 obesity (BMI 25 to 45 kg/m2).

Exclusion Criteria:

1) cystathionine beta-synthase (CBS deficiency);
2) Presence of liver disease other than NAFLD;
3) Use of medications causing steatosis;
4) Known alcohol consumption ≥ 2 drink per day;
5) Use of medications known to cause insulin resistance;
6) Use of weight loss drugs (or program) within 3 months of screening;
7) Treatment with any experimental drug within the past 6 months;
8) Subjects must be willing to abstain from use of phosphodiesterase type 5 (PDE-5) inhibitors;
9) Pregnancy or lactation, and women of child bearing potential must use adequate contraception;
10) Surgery within 30 days of screening;
11) 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;
12) Uncontrolled hypertension;
13) eGFR <60; 14) History of acquired immune deficiency syndrome;
15) History of malignancy within 5 years;
16) Hemoglobin <12 g/dL (males), <10 g/dL (females);
17) Triglycerides (TG) >500 mg/dL;
18) Poor mental function or any other reason to expect patient difficulty in complying with study requirements;
19) Metal clips or implants that preclude magnetic resonance imaging.

Sites / Locations

Joslin Diabetes Center and Brigham and Womens Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Betaine

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Fasting and 2 Hour Glucose Levels, Comparing 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)

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

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

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

Insulin Sensitivity

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

Secondary Outcome Measures

Full Information

NCT ID

NCT01950039

First Posted

September 16, 2013

Last Updated

March 25, 2021

Sponsor

Joslin Diabetes Center

Collaborators

American Diabetes Association

1. Study Identification

Unique Protocol Identification Number

NCT01950039

Brief Title

Metabolic Effects of Betaine Supplementation

Official Title

Bedside to Bench and Back: Cardiometabolic Effects of Betaine Supplementation

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Completed

Study Start Date

January 2014 (undefined)

Primary Completion Date

December 2017 (Actual)

Study Completion Date

August 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Joslin Diabetes Center

Collaborators

American Diabetes Association

4. Oversight

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obesity, Dysglycemia

Keywords

Obesity, Glucose Intolerance

7. Study Design

Primary Purpose

Other

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Betaine

Arm Type

Active Comparator

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Betaine

Other Intervention Name(s)

trimethyl glycine

Intervention Description

Betaine or placebo administered orally in divided doses over 12 weeks

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo administered orally in divided doses over 3 months

Primary Outcome Measure Information:

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

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

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

Title

Endothelial Function

Description

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

Time Frame

baseline and 12 weeks

Title

Insulin Sensitivity

Description

Time Frame

Baseline and 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 1) Men and women aged 21-65 years old; 2) 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%); 3) overweight to grade 3 obesity (BMI 25 to 45 kg/m2). Exclusion Criteria: 1) cystathionine beta-synthase (CBS deficiency); 2) Presence of liver disease other than NAFLD; 3) Use of medications causing steatosis; 4) Known alcohol consumption ≥ 2 drink per day; 5) Use of medications known to cause insulin resistance; 6) Use of weight loss drugs (or program) within 3 months of screening; 7) Treatment with any experimental drug within the past 6 months; 8) Subjects must be willing to abstain from use of phosphodiesterase type 5 (PDE-5) inhibitors; 9) Pregnancy or lactation, and women of child bearing potential must use adequate contraception; 10) Surgery within 30 days of screening; 11) 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; 12) Uncontrolled hypertension; 13) eGFR <60; 14) History of acquired immune deficiency syndrome; 15) History of malignancy within 5 years; 16) Hemoglobin <12 g/dL (males), <10 g/dL (females); 17) Triglycerides (TG) >500 mg/dL; 18) Poor mental function or any other reason to expect patient difficulty in complying with study requirements; 19) Metal clips or implants that preclude magnetic resonance imaging.

Facility Information:

Facility Name

Joslin Diabetes Center and Brigham and Womens Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

29860335

Citation

Grizales AM, Patti ME, Lin AP, Beckman JA, Sahni VA, Cloutier E, Fowler KM, Dreyfuss JM, Pan H, Kozuka C, Lee A, Basu R, Pober DM, Gerszten RE, Goldfine AB. Metabolic Effects of Betaine: A Randomized Clinical Trial of Betaine Supplementation in Prediabetes. J Clin Endocrinol Metab. 2018 Aug 1;103(8):3038-3049. doi: 10.1210/jc.2018-00507.

Results Reference

result

Learn more about this trial

Metabolic Effects of Betaine Supplementation

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