Clinical trial NCT02022280: Effect of Proton Pump Inhibitors on Endothelial Function
Official title: Do Proton Pump Inhibitors (PPIs) Increase Cardiovascular Risk? Effect of PPIs on Endothelial Function and ADMA.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Endothelial Dysfunction
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2013-12-27
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in reactive hyperemia index as measured by peripheral arterial tonometry (EndoPAT)
timeFrame: Baseline, 1 week, 5 weeks, 7 weeks, 11 weeks, 12 weeks
Secondary outcomes:
measure: Change in blood ADMA level
timeFrame: Baseline, 1 week, 5 weeks, 7 weeks, 11 weeks, 12 weeks
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Nicholas Leeper, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.