Metabolic Effects of Betaine Supplementation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Bedside to Bench and Back: Cardiometabolic Effects of Betaine Supplementation

Conditions
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Obesity, Dysglycemia

Intervention / Treatment
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* Drug: Betaine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Betaine<br> | Drug: Betaine<br>* Betaine or placebo administered orally in divided doses over 12 weeks<br>* Other names: trimethyl glycine;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo administered orally in divided doses over 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline and 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. | baseline and 12 weeks | 
| 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). | baseline and 12 weeks | 
| Endothelial Function | Brachial artery reactivity to flow and nitroglycerin stimuli, assessed as percent change from baseline | baseline and 12 weeks | 
| 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 | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Glucose Intolerance