Efficacy of Zinc L-carnosine in Maintaining Remission of Gastroesophageal Reflux Disease (GERDILOR)

Efficacy of Zinc L-carnosine (Hepilor®) in Maintaining Remission of Gastroesophageal Reflux Disease: a Randomised, Double-blind, Placebo-controlled Study

Gastroesophageal reflux disease (GERD), according to the Montreal classification, is defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. GERD, as clinically defined by the presence of heartburn, acid regurgitation, or both, at least once a week, is a global disease, being one of the most common gastroenterological disorders worldwide that affects roughly 10-30% of the general population in the Western world and less than 10% of the Asian populations. GERD complications may be life threatening and range from reflux esophagitis to Barrett's oesophagus and, eventually, adenocarcinoma.

Zinc L-carnosine (brand name in Italy: Hepilor®) is a chelate compound of zinc and L-carnosine, with a long history of more than 20 years of clinical use in Japan that has recently become available in Italy for the treatment of any condition that requires a mucosal protection and mucosal repair within the gastrointestinal tract, thus including GERD. However, clinical data in western countries are limited. The aim of this double-blind, placebo-controlled study is to demonstrate the efficacy of Zinc-l-carnosine in maintaining GERD clinical remission during a 12-week treatment.

Study Overview

• Status: Unknown
• Conditions: Gastroesophageal Reflux Disease
• Intervention / Treatment: Other: Placebo; Drug: Zinc-l-carnosine

Detailed Description

The investigators hypothesise that Zinc-l-carnosine is able to maintain GERD remission, thus improving the quality of life of these patients. A comparison with a placebo is necessary, as GERD symptoms may be heavily influenced by the nocebo/placebo effect.

This is a post-marketing, single center, double-blind, and randomized, placebo-controlled, parallel study. Patients with GERD treated with an 8-week cours of proton pump inhibitors will be randomize and receive either Zinc-l-carnosine or placebo for 12-week. GERD symptoms will be assessed with a questionnaire (modified GERD questionnaire by Locke) monthly for 12 weeks and after a 4-week wash-out. Also, quality of life will be assessed at baseline and at 12 weeks with the 36-item short form survey (SF-36).

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Antonio Di Sabatino, MD; Phone Number: 00390382502973; Email: a.disabatino@smatteo.pv.it

Study Locations

• Italy
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione IRCCS Policlinico San Matteo
    • Contact: Antonio Di Sabatino, MD; Phone Number: 00390382501596; Email: a.disabatino@smatteo.pv.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• written informed consent to participate
• be male or female patients ≥ 18 years old, with an established diagnosis of GERD
• have a diagnosis of GERD that is established clinically in case of typical symptoms (heartburn and acid regurgitation ≥ once weekly) or with 24-hour esophageal impedence monitoring in case of atypical symptoms not responsive to proton pump inhibitors (PPIs) or in case of unclear diagnosis
• have been treated with an 8-week course of PPI (as per gold-standard treatment of GERD) before entering the study

Exclusion Criteria:

• any medical condition that requires chronic therapy with PPIs or H2 antagonists; anti-acid agents must be discontinued within the study period
• oesophageal motility disorders

• allergy or intolerance to Hepilor® (it contains parahydroxybenzoate that may cause allergies)

  • inconclusive diagnosis of GERD and related symptoms
  • patients with active H. pylori infection (diagnosed with any of the available tests)
  • previous major oesophageal surgery
  • history of any advanced/relevant organ dysfunction, in particular chronic kidney disease, chronic liver disease of any aetiology, hearth failure
  • any concomitant medical condition with a poor prognosis (< 3 months)
  • pregnant females
  • inability to conform to the protocol
  • treatment with any investigational drug within the previous 3 months
  • any subject not able to express/understand the informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Zinc-l-carnosine, liquid oral formulation, 75mg twice daily (20mL, using the measuring cup, twice daily), to be swallowed on an empty stomach (waiting at least one hour from the last meal).	Drug: Zinc-l-carnosine; Patients will be asked to take the investigational product as already mentioned (blindly).
Placebo Comparator: B; Placebo, liquid oral formulation, 75mg twice daily (20mL, using the measuring cup, twice daily), to be swallowed on an empty stomach (waiting at least one hour from the last meal).	Other: Placebo; Patients will be asked to take placebo as already mentioned (blindly).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastroesophageal reflux disease (GERD) remission	GERD remission will be assessed according to the modified GERD questionnaire by Locke et al. GERD remission is established if any mild symptom does not occur 2 or more days a week, or if any moderate/severe symptom does not occur more than one day a week.	4 weeks
Gastroesophageal reflux disease (GERD) remission	GERD remission will be assessed according to the modified GERD questionnaire by Locke et al. GERD remission is established if any mild symptom does not occur 2 or more days a week, or if any moderate/severe symptom does not occur more than one day a week.	8 weeks
Gastroesophageal reflux disease (GERD) remission	GERD remission will be assessed according to the modified GERD questionnaire by Locke et al. GERD remission is established if any mild symptom does not occur 2 or more days a week, or if any moderate/severe symptom does not occur more than one day a week.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
36 item short form health survey	Quality of life will be assessed with SF-36 at baseline and after 12 weeks of treatment. The difference between the two groups will be compared at the end of treatment.	12 weeks
Sustained GERD remission	GERD remission will be assessed according to the modified GERD questionnaire by Locke et al. after a 4-week wash-out (week 16). GERD remission is established if any mild symptom does not occur 2 or more days a week, or if any moderate/severe symptom does not occur more than one day a week.	16 weeks

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Matteo

Publications and helpful links

General Publications

• Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology. 1997 May;112(5):1448-56. doi: 10.1016/s0016-5085(97)70025-8.
• Locke GR, Talley NJ, Weaver AL, Zinsmeister AR. A new questionnaire for gastroesophageal reflux disease. Mayo Clin Proc. 1994 Jun;69(6):539-47. doi: 10.1016/s0025-6196(12)62245-9.
• Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006 Aug;101(8):1900-20; quiz 1943. doi: 10.1111/j.1572-0241.2006.00630.x.
• Arakawa T, Satoh H, Nakamura A, Nebiki H, Fukuda T, Sakuma H, Nakamura H, Ishikawa M, Seiki M, Kobayashi K. Effects of zinc L-carnosine on gastric mucosal and cell damage caused by ethanol in rats. Correlation with endogenous prostaglandin E2. Dig Dis Sci. 1990 May;35(5):559-66. doi: 10.1007/BF01540402.

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2018
• Primary Completion (Anticipated): April 1, 2020
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: March 5, 2018
• First Submitted That Met QC Criteria: March 9, 2018
• First Posted (Actual): March 16, 2018

Study Record Updates

• Last Update Posted (Actual): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: heartburn; regurgitation; pyrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Esophagitis; Peptic Ulcer; Duodenal Diseases; Gastroesophageal Reflux; Esophagitis, Peptic; Gastrointestinal Agents; Anti-Ulcer Agents; Polaprezinc
• Other Study ID Numbers: GERDILOR17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All individual participant data (IPD), anonymized and aggregated, that underlie results in a publication.
• IPD Sharing Time Frame: Only on future articles that will be published.
• IPD Sharing Supporting Information Type: Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No