GastroparesisPhase 1NCT02232308
Modulation of Heme Oxygenase 1 by Nizatidine and Lisinopril in Healthy Subjects
A Phase 1 study testing Nizatidine and Lisinopril in people with Gastroparesis, run by Adil Bharucha at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Gastroparesis
- What is being tested?
- Nizatidine and Lisinopril
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2014to Sep 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Pregnant
- Breast feeding
- Current smoker
- Symptoms of functional GI disorder as assessed by a validated questionnaire
- Previous history of peptic ulcer disease.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Mayo Clinic
Rochester, Minnesota, 55905
About this study
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.
Read the 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.
- Conditions
- Gastroparesis
- Being tested
- Nizatidine, Lisinopril, Placebo
- Medical subject headings
- Gastroparesis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NizatidineDrug
Also called Axid
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.
LisinoprilDrug
Also called Zestril, Prinivil
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Nizatidine | Experimental | 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. Receives: Drug: Nizatidine |
| Lisinopril | Experimental | 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. Receives: Drug: Lisinopril |
| Nizatidine plus Lisinopril | Experimental | 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. Receives: Drug: Nizatidine; Drug: Lisinopril |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma heme oxygenase 1 (HO-1) protein concentration
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.
Measured: Day 3, Day 10
Change in Monocyte HO-1 activity
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.
Measured: Day 3, Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2014 (estimated)
- Study startJul 2014
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GastroparesisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Adil Bharucha
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Research Resources (NCRR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor-investigator, Adil Bharucha, Mayo Clinic
- Investigators
- Adil Bharucha, MBBS, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02232308
- Sponsor's protocol ID
- 14-004137
- Other IDs
- UL1RR024150, P01DK068055
- Status last verified
- Apr 2015
- First submitted
- 23 Jun 2014
- Last updated
- 30 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Heme Oxygenase 1 by Nizatidine and Lisinopril in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02232308
- Acronym / sponsor ID
- 14-004137
- Conditions
- Gastroparesis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Adil BharuchaUniversity, hospital or other
- Collaborators
- National Center for Research Resources (NCRR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jul 2014
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 5 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Nizatidine | Experimental | Drug: NizatidineNizatidine (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 | Experimental | Drug: LisinoprilLisinopril (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 | Experimental | Drug: Nizatidine, Drug: LisinoprilNizatidine (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. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- Pregnant
- Breast feeding
- Current smoker
- Symptoms of functional GI disorder as assessed by a validated questionnaire
- Previous history of peptic ulcer disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NizatidineAlso: AxidNizatidine (150 mg) will be administered once daily for the first 3 days, then twice daily for days 4-9, and once on day 10. | Drug | Nizatidine, Nizatidine plus Lisinopril |
| LisinoprilAlso: Zestril, PrinivilLisinopril (10 mg) will be administered once daily for the first 3 days, then twice daily for days 4-9, and once on day 10. | Drug | Lisinopril, Nizatidine plus Lisinopril |
| PlaceboPlacebo 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. | Drug | Placebo |
Primary outcome
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adil Bharucha, MBBS, MD principal investigator
Mayo Clinic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nizatidine and Lisinopril in people with Gastroparesis, run by Adil Bharucha at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in plasma heme oxygenase 1 (HO-1) protein concentration (time frame: Day 3, Day 10). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2015.