Skip to main content
OpenTrials
Completed

NCT Number: NCT02232308

Modulation of Heme Oxygenase 1 by Nizatidine and Lisinopril in Healthy Subjects

To assess if oral nizatidine or lisinopril alone and in combination will increase heme oxygenase 1 (HO-1) protein concentration and activity compared to placebo in healthy subjects.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Gastroparesis Digestive System Diseases Gastrointestinal Diseases Neurologic Manifestations Paralysis Pathological Conditions, Signs and Symptoms Signs and Symptoms Stomach Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Mayo Clinic, Rochester, Minnesota, United States

Loading trial locations.

About this study

Current therapeutic options for gastroparesis are limited to dietary modifications and pharmacological (i.e., prokinetic and symptomatic) agents. Exciting and novel preliminary data from our programs demonstrate that (i) reduced expression of heme oxygenase 1 (HO-1) is responsible for loss of interstitial cells of Cajal and delayed gastric emptying in non-obese diabetic (NOD) mice, (ii) upregulation of (HO-1) reverses delayed gastric emptying in this model, perhaps by generating carbon monoxide (CO), which has anti-apoptotic and cytoprotective actions, and may relax smooth muscle, and (iii) hemin upregulates HO-1 in humans. However, hemin is exorbitant and can only be administered intravenously. A large throughput screening assay uncovered that the histamine H2 receptor antagonist nizatidine and the ACE inhibitor lisinopril upregulate HO-1 in Human Embryonic Kidney (HEK) cells. Hence, this double-blind placebo-controlled study will randomly assign 24 healthy subjects to one of 4 arms, and HO-1 protein activity and concentration will be assessed.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy subjects without clinical evidence of significant cardiovascular, gastrointestinal, hematological, neurological, psychiatric or other disease that may interfere with the objectives of the study and/or pose safety concerns
  • Normal serum potassium and estimated glomerular filtration rate (eGFR) > 60 ml/minute
  • Baseline systolic BP ≥ 110 mmHg
  • No known hypersensitivity to lisinopril or nizatidine
  • Able to provide written informed consent before participating in the study
  • Able to communicate adequately with the investigator and to comply with the requirements for the entire study.

Exclusion criteria

  • Pregnant
  • Breast feeding
  • Current smoker
  • Symptoms of functional GI disorder as assessed by a validated questionnaire
  • Previous history of peptic ulcer disease.

Treatment and study plan

Nizatidine

Drug

Nizatidine (150 mg) will be administered once daily for the first 3 days, then twice daily for days 4-9, and once on day 10.

Other names: Axid

Lisinopril

Drug

Lisinopril (10 mg) will be administered once daily for the first 3 days, then twice daily for days 4-9, and once on day 10.

Other names: Zestril, Prinivil

Placebo

Drug

Placebo capsules to match active drug will be administered once daily for the first 3 days, then twice daily for days 4-9, and once on day 10.

Primary outcomes

  1. Change in plasma heme oxygenase 1 (HO-1) protein concentration

    Time frame: Day 3, Day 10

    Heme oxygenase (HO-1) degrades heme and protects against oxidative stress. HO-1 concentration was measured by a blood test; the units are ng/ml.

  2. Change in Monocyte HO-1 activity

    Time frame: Day 3, Day 10

    Heme oxygenase (HO-1) degrades heme and protects against oxidative stress. When HO-1 is induced, more heme is removed, and end products of heme metabolism (i.e., carbon monoxide, iron, and bilirubin) are generated. HO-1 activity was measured by a blood test, the units are pmol bilirubin/mg/h.

Sponsors and collaborators

Lead sponsor

Adil Bharucha

Other

Collaborators

  • National Center for Research Resources (NCRR)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Important dates

Study start
2014
Primary completion
2014
Study completion
2014
First posted
Sep 5, 2014
Registry last updated
Apr 30, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.