Modulation of Heme Oxygenase 1 by Nizatidine and Lisinopril in Healthy Subjects
- Registration Number
- NCT02232308
- Lead Sponsor
- Adil Bharucha
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo 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. Nizatidine Nizatidine 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. Lisinopril Lisinopril 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. Nizatidine plus Lisinopril Nizatidine Nizatidine (150 mg) and 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. Nizatidine plus Lisinopril Lisinopril Nizatidine (150 mg) and 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.
- Primary Outcome Measures
Name Time Method Change in plasma heme oxygenase 1 (HO-1) protein concentration 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.
Change in Monocyte HO-1 activity 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (2)
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States