Clinical trial NCT02232308: Modulation of Heme Oxygenase 1 by Nizatidine and Lisinopril in Healthy Subjects
Official title: Modulation of Heme Oxygenase 1 by Nizatidine and Lisinopril in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastroparesis
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Center for Research Resources (NCRR)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2014-09-05
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in plasma heme oxygenase 1 (HO-1) protein concentration
timeFrame: Day 3, Day 10
measure: Change in Monocyte HO-1 activity
timeFrame: Day 3, Day 10
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Adil Bharucha, MBBS, MD
role: PRINCIPAL_INVESTIGATOR
References: