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

Study Overview
=================
Brief Summary
-----------------
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.

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).

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

Conditions
-----------------
Gastroesophageal Reflux Disease

Intervention / Treatment
-----------------
* Drug: Zinc-l-carnosine
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>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<br>* Patients will be asked to take the investigational product as already mentioned (blindly).<br>|
| Placebo Comparator: B<br>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<br>* Patients will be asked to take placebo as already mentioned (blindly).<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
heartburn, pyrosis, regurgitation