Effect of Proton Pump Inhibitors on Endothelial Function

Study Overview
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Brief Summary
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In this randomized controlled crossover study, the investigators propose to test the hypothesis that proton pump inhibitors (PPIs) increase plasma levels of asymmetric dimethylarginine (ADMA), which is a marker of endothelial dysfunction. The authors propose to evaluate ADMA concentrations and vascular function analysis in healthy volunteers and adults with a history of cardiovascular disease given PPI vs placebo for four weeks each.

Official Title
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Do Proton Pump Inhibitors (PPIs) Increase Cardiovascular Risk? Effect of PPIs on Endothelial Function and ADMA.

Conditions
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Endothelial Dysfunction

Intervention / Treatment
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* Drug: Lansoprazole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female volunteers aged 18 to 75 years (n=10) or male or female volunteers with a history of coronary or peripheral artery disease (n=10) Able to understand the nature of the study and to give written informed consent Able to communicate well with the investigator himself or his/her representatives Body Mass Index between 18 kg/m^2 and 35 kg/m^2 at the screening visit Creatinine <1.5, and liver enzymes <2x normal, with all laboratory tests considered normal or of no significant clinical relevance to the study by the investigator Exclusion Criteria: Contra-indication to proton pump inhibitor treatment Current treatment with PPI or H2 antagonist, and not able to tolerate withdrawal or washout of medication. Current or historical evidence of clinically severe cardiovascular, neurological, hematological, hepatic, gastrointestinal, renal, pulmonary, endocrinological, metabolic or psychiatric disease. Any other acute or chronic disease which could influence the volunteer's health and/or the study results Presence or history of malabsorption or any gastrointestinal surgery except appendectomy or hernia repair Use of enzyme inducers or enzyme inhibitor drugs within the last three months before the first drug administration Participation in another ongoing clinical trial Past or current drug exposure amounting to drug abuse or addiction Past or current alcohol exposure amounting to alcohol abuse or addiction (i.e. > 28 units per week for males, where 1 unit = one measure of spirit (25 mL), one glass of wine (125 mL) or 1/2 pint beer) Donation of blood or any other major blood loss (>500 mL) within three months before the study Unwilling or unable to comply with the study protocol for any reason or in the opinion of the investigator should not participate in the study Positive test for hepatitis B surface antigen, hepatitis C antibody, HIV-1 or HIV-2 antibody at screening Known allergy or intolerance to any other compound in the study drug or any other closely related compound

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proton Pump Inhibitor<br>Lansoprazole (Prevacid) | Drug: Lansoprazole<br> <br> * Other names: Prevacid;|
| Placebo Comparator: Vitamin pill<br> | Drug: Placebo<br>* Vitamin pill<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in reactive hyperemia index as measured by peripheral arterial tonometry (EndoPAT) |  | Baseline, 1 week, 5 weeks, 7 weeks, 11 weeks, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood ADMA level |  | Baseline, 1 week, 5 weeks, 7 weeks, 11 weeks, 12 weeks |