Effect of Proton Pump Inhibitors on Endothelial Function (PPI)

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

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.

Study Overview

• Status: Completed
• Conditions: Endothelial Dysfunction
• Intervention / Treatment: Drug: Lansoprazole; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Proton Pump Inhibitor; Lansoprazole (Prevacid)	Drug: Lansoprazole; Other Names: Prevacid
Placebo Comparator: Vitamin pill	Drug: Placebo; Vitamin pill

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Nicholas Leeper, MD, Stanford University

Publications and helpful links

General Publications

• Ghebremariam YT, Cooke JP, Khan F, Thakker RN, Chang P, Shah NH, Nead KT, Leeper NJ. Proton pump inhibitors and vascular function: A prospective cross-over pilot study. Vasc Med. 2015 Aug;20(4):309-16. doi: 10.1177/1358863X14568444. Epub 2015 Apr 2.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2013
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: December 3, 2013
• First Submitted That Met QC Criteria: December 20, 2013
• First Posted (Estimate): December 27, 2013

Study Record Updates

• Last Update Posted (Actual): August 23, 2022
• Last Update Submitted That Met QC Criteria: August 19, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole
• Other Study ID Numbers: 23848; 1144447-121-DHAXB (Other Grant/Funding Number: Stanford Translational Research and Applied Medicine)