ECL-cell HyperplasiaPhase 1NCT02620696
Effect of Netazepide on Omeprazole-induced Changes in Chromogranin A and Gastrin
A Phase 1 study testing netazepide in people with ECL-cell Hyperplasia and Parietal-cell Hyperplasia, run by Trio Medicines Ltd..
Trial summary
Hypergastrinaemia induced by proton pump inhibitor (PPI) treatment is reported to cause ECL-cell and parietal-cell hyperplasia, and rebound hyperacidity and dyspepsia after PPI withdrawal. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- ECL-cell Hyperplasia, Parietal-cell Hyperplasia, Rebound Hyperacidity
- What is being tested?
- netazepide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- No sites listed yet
- Study dates
- Nov 2009to Sep 2010
- 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy men, post-menopausal women or pre-menopausal women, using one of the following methods of contraception: abstinence; condom and spermicide; intra-uterine device; or hysterectomy or tubal ligation
- Age 18-75 years
- A body mass index (Quetelet index) in the range 18.0-30.9 Body Mass Index = weight (kg)/height (m2)
- Negative test for H. pylori
- No history of dyspepsia symptoms
- No history of peptic ulcer or oesophagitis
Show all 11Show fewer
- No history of treatment with a histamine H2 antagonist, proton pump inhibitor or antacid
- Normal serum gastrin (no greater than 5% above the upper limit of the HMR laboratory reference range for gastrin)
- Non-smokers or social smokers (defined as 10 or fewer cigarettes per week)
- Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial
- Willingness to give written consent to participate after reading the Information and Consent Form, and after having the opportunity to discuss the trial with the investigator or delegate.
Who cannot join
- Women who are pregnant or lactating.
- Clinically relevant abnormal history, physical findings, ECG (> 450 msec), or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.
- Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the subject's participation in the trial or make it unnecessarily hazardous.
- Severe adverse reaction to any drug
- Use, during the 14 days before the baseline visit, of a prescription medicine, especially one that inhibits or induces CYP3A4/5, CYP2C8 or CYP2C9, a hormone contraceptive and hormone replacement therapy.
- Use, during the 14 days before the baseline visit, of herbal products, such as St John's wort.
Show all 9Show fewer
- Use of an over-the-counter medicine during the 7 days before the baseline visit, with the exception of paracetamol (up to 4 g daily).
- Participation in another trial of a new chemical entity or a prescription medicine, or loss of more than 400 mL blood, within the previous 3 months.
- Presence or history of drug or alcohol abuse.
About this study
Official title: Effect of Netazepide, a Gastrin/CCK2 Receptor Antagonist, on Esomeprazole-induced Increases in Circulating Gastrin and Chromogranin A, and on Esomeprazole Withdrawal in Healthy Subjects
Hypergastrinaemia induced by proton pump inhibitor (PPI) treatment is reported to cause ECL-cell and parietal-cell hyperplasia, and rebound hyperacidity and dyspepsia after PPI withdrawal.
The objective of the study was to determine the dosage regimen of netazepide, a gastrin/CCK2 receptor antagonist, required to inhibit the trophic effects of PPI-induced hypergastrinaemia.
Six groups of 8 healthy subjects participated in a randomised, double-blind, placebo-controlled exploratory study of esomeprazole 40 mg daily for 28 days, and netazepide 1, 5 or 25 mg, or placebo daily during the last 14 days of esomeprazole dosing, or 14 days after esomeprazole withdrawal. Serum gastrin and plasma chromogranin A (CgA) were measured regularly from study start until at least 1 week after the last dose. Dyspepsia was monitored after esomeprazole withdrawal.
Read the detailed description
Non-clinical studies have shown that PPI-induced hypergastrinaemia leads to rebound gastric hyperacidity after PPI withdrawal. A gastrin/CCK2 receptor antagonist inhibits that response. Studies in healthy subjects and patients also suggest that PPI withdrawal leads to rebound hyperacidity, but the evidence is controversial. However, there is better evidence from studies in healthy subjects that PPI withdrawal can lead to dyspepsia.
The principal aims of this study were: to assess the effect of different dose regimens of netazepide on the increases in circulating gastrin and CgA induced by esomeprazole in healthy subjects; and to choose a dose regimen for future studies of esomeprazole withdrawal in patients. The secondary aims were: to assess if omeprazole withdrawal leads to dyspepsia, and if so whether it can be prevented by netazepide; and to assess the likelihood of an interaction between esomeprazole and netazepide. Gastrin and CgA are biomarkers of acid suppression and increased ECL-cell activity, respectively.
This was a randomised, double-blind, placebo-controlled, parallel-group, pilot study, in which six groups of eight healthy subjects took esomeprazole 40 mg daily for 28 days, and netazepide 1, 5 or 25 mg, or placebo, daily during the last 14 days of esomeprazole dosing, or the 14 days immediately following esomeprazole withdrawal (25 mg only). Gastrin and CgA were measured before the start of dosing until at least one week after completion of dosing.
- Being tested
- netazepide
- Medical subject headings
- Dyspepsia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
netazepideDrug
Also called YF476
| Study group | Role | What they receive |
|---|---|---|
| Treatment 1 | Experimental | * esomeprazole 40 mg daily for 28 days (Days 1-28)
* netazepide placebo daily from Days 1-42 Receives: Drug: netazepide |
| Treatment 2 | Experimental | * esomeprazole 40 mg daily for 28 days (Days 1-28)
* netazepide 25 mg daily for 14 days (Days 15-28)
* netazepide placebo daily from Days 1-14, and from Days 29-42 Receives: Drug: netazepide |
| Treatment 3 | Experimental | * esomeprazole 40 mg daily for 28 days (Days 1-28)
* netazepide 25 mg daily for 14 days (Days 29-42)
* netazepide placebo daily from Days 1-28 Receives: Drug: netazepide |
| Treatment 4 | Experimental | * esomeprazole 40 mg daily for 28 days (Days 1-28)
* netazepide placebo daily from Days 1-28 Receives: Drug: netazepide |
| Treatment 5 | Experimental | * esomeprazole 40 mg daily for 28 days (Days 1-28)
* netazepide 1 mg daily for 14 days (Days 15-28)
* netazepide placebo daily from Days 1-14 Receives: Drug: netazepide |
| Treatment 6 | Experimental | * esomeprazole 40 mg daily for 28 days (Days 1-28)
* netazepide 5 mg daily for 14 days (Days 15-28)
* netazepide placebo daily from Days 1-14 Receives: Drug: netazepide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma chromogranin A (CgA) concentrations
We separated serum or plasma from blood, and stored samples at -20°C until assay by ELISA (serum gastrin: Immulite 2000, DPC. CV = 6.9%; plasma CgA: DAKO. CV = 7.2%) and validated HPLC/MS method (plasma netazepide: lower limit of quantification 0.5 ng/mL) (Redrup et al 2002).
Measured: 8 weeks
Serum gastrin concentrations
We separated serum or plasma from blood, and stored samples at -20°C until assay by ELISA (serum gastrin: Immulite 2000, DPC. CV = 6.9%; plasma CgA: DAKO. CV = 7.2%) and validated HPLC/MS method (plasma netazepide: lower limit of quantification 0.5 ng/mL) (Redrup et al 2002).
Measured: 8 weeks
Secondary outcomes (4)
Dyspepsia scores
The dyspepsia questionnaire uses 4- or 5-point Likert scales to measure frequency and severity of 15 upper gastrointestinal symptoms, and the bother they cause (Talley et al 2001).
Measured: 8 weeks
Antacid usage
Participants reported antacid usage.
Measured: 8 weeks
Safety assessed by Vital signs, ECG variables, physical examinations, laboratory variables
Measured: 5 weeks
Tolerability assessed by Adverse events
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2015 (estimated)
- Study startNov 2009
- Primary completionSep 2010
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ECL-cell HyperplasiaStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Trio Medicines Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Malcolm Boyce, Principal investigator, Hammersmith Medicines Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02620696
- Sponsor's protocol ID
- T-013
- Status last verified
- Dec 2015
- First submitted
- 1 Dec 2015
- Last updated
- 3 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Netazepide, a Gastrin/CCK2 Receptor Antagonist, on Esomeprazole-induced Increases in Circulating Gastrin and Chromogranin A, and on Esomeprazole Withdrawal in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02620696
- Acronym / sponsor ID
- T-013
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Trio Medicines Ltd.Industry (pharma, biotech, devices)
- Study start
- Nov 2009
- Primary completion
- Sep 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 3 Dec 2015 (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.
Hypergastrinaemia induced by proton pump inhibitor (PPI) treatment is reported to cause ECL-cell and parietal-cell hyperplasia, and rebound hyperacidity and dyspepsia after PPI withdrawal.
The objective of the study was to determine the dosage regimen of netazepide, a gastrin/CCK2 receptor antagonist, required to inhibit the trophic effects of PPI-induced hypergastrinaemia.
Six groups of 8 healthy subjects participated in a randomised, double-blind, placebo-controlled exploratory study of esomeprazole 40 mg daily for 28 days, and netazepide 1, 5 or 25 mg, or placebo daily during the last 14 days of esomeprazole dosing, or 14 days after esomeprazole withdrawal. Serum gastrin and plasma chromogranin A (CgA) were measured regularly from study start until at least 1 week after the last dose. Dyspepsia was monitored after esomeprazole withdrawal.
Detailed description
Non-clinical studies have shown that PPI-induced hypergastrinaemia leads to rebound gastric hyperacidity after PPI withdrawal. A gastrin/CCK2 receptor antagonist inhibits that response. Studies in healthy subjects and patients also suggest that PPI withdrawal leads to rebound hyperacidity, but the evidence is controversial. However, there is better evidence from studies in healthy subjects that PPI withdrawal can lead to dyspepsia.
The principal aims of this study were: to assess the effect of different dose regimens of netazepide on the increases in circulating gastrin and CgA induced by esomeprazole in healthy subjects; and to choose a dose regimen for future studies of esomeprazole withdrawal in patients. The secondary aims were: to assess if omeprazole withdrawal leads to dyspepsia, and if so whether it can be prevented by netazepide; and to assess the likelihood of an interaction between esomeprazole and netazepide. Gastrin and CgA are biomarkers of acid suppression and increased ECL-cell activity, respectively.
This was a randomised, double-blind, placebo-controlled, parallel-group, pilot study, in which six groups of eight healthy subjects took esomeprazole 40 mg daily for 28 days, and netazepide 1, 5 or 25 mg, or placebo, daily during the last 14 days of esomeprazole dosing, or the 14 days immediately following esomeprazole withdrawal (25 mg only). Gastrin and CgA were measured before the start of dosing until at least one week after completion of dosing.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Treatment 1 | Experimental | Drug: netazepide* esomeprazole 40 mg daily for 28 days (Days 1-28) * netazepide placebo daily from Days 1-42 |
| Treatment 2 | Experimental | Drug: netazepide* esomeprazole 40 mg daily for 28 days (Days 1-28) * netazepide 25 mg daily for 14 days (Days 15-28) * netazepide placebo daily from Days 1-14, and from Days 29-42 |
| Treatment 3 | Experimental | Drug: netazepide* esomeprazole 40 mg daily for 28 days (Days 1-28) * netazepide 25 mg daily for 14 days (Days 29-42) * netazepide placebo daily from Days 1-28 |
| Treatment 4 | Experimental | Drug: netazepide* esomeprazole 40 mg daily for 28 days (Days 1-28) * netazepide placebo daily from Days 1-28 |
| Treatment 5 | Experimental | Drug: netazepide* esomeprazole 40 mg daily for 28 days (Days 1-28) * netazepide 1 mg daily for 14 days (Days 15-28) * netazepide placebo daily from Days 1-14 |
| Treatment 6 | Experimental | Drug: netazepide* esomeprazole 40 mg daily for 28 days (Days 1-28) * netazepide 5 mg daily for 14 days (Days 15-28) * netazepide placebo daily from Days 1-14 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Healthy men, post-menopausal women or pre-menopausal women, using one of the following methods of contraception: abstinence; condom and spermicide; intra-uterine device; or hysterectomy or tubal ligation
- Age 18-75 years
- A body mass index (Quetelet index) in the range 18.0-30.9 Body Mass Index = weight (kg)/height (m2)
- Negative test for H. pylori
- No history of dyspepsia symptoms
Key exclusion criteria (9 listed)
- Women who are pregnant or lactating.
- Clinically relevant abnormal history, physical findings, ECG (> 450 msec), or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.
- Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the subject's participation in the trial or make it unnecessarily hazardous.
- Severe adverse reaction to any drug
- Use, during the 14 days before the baseline visit, of a prescription medicine, especially one that inhibits or induces CYP3A4/5, CYP2C8 or CYP2C9, a hormone contraceptive and hormone replacement therapy.
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 |
|---|---|---|
| netazepideAlso: YF476 | Drug | Treatment 1, Treatment 2, Treatment 3, Treatment 4, Treatment 5, Treatment 6 |
Primary outcome
Plasma chromogranin A (CgA) concentrations
Time frame: 8 weeks
We separated serum or plasma from blood, and stored samples at -20°C until assay by ELISA (serum gastrin: Immulite 2000, DPC. CV = 6.9%; plasma CgA: DAKO. CV = 7.2%) and validated HPLC/MS method (plasma netazepide: lower limit of quantification 0.5 ng/mL) (Redrup et al 2002).
Serum gastrin concentrations
Time frame: 8 weeks
We separated serum or plasma from blood, and stored samples at -20°C until assay by ELISA (serum gastrin: Immulite 2000, DPC. CV = 6.9%; plasma CgA: DAKO. CV = 7.2%) and validated HPLC/MS method (plasma netazepide: lower limit of quantification 0.5 ng/mL) (Redrup et al 2002).
4 secondary outcomes
Dyspepsia scores
Time frame: 8 weeks
Antacid usage
Time frame: 8 weeks
Safety assessed by Vital signs, ECG variables, physical examinations, laboratory variables
Time frame: 5 weeks
Tolerability assessed by Adverse events
Time frame: 8 weeks
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 3 Dec 2015.
- Individual participant dataSharing planned: No
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.
Malcolm Boyce principal investigator
Hammersmith Medicines Research
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing netazepide in people with ECL-cell Hyperplasia and Parietal-cell Hyperplasia, run by Trio Medicines Ltd..
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 11 inclusion and 9 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 3 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
Plasma chromogranin A (CgA) concentrations (time frame: 8 weeks). 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 3 Dec 2015.