## Protocol Section
### Identification Module
**NCT ID:** NCT00222079

**Brief Title:** Evaluation of Esomeprazole in Treating Gastro-esophageal Reflux Disease (GERD) in Head and Neck Cancer Patients Exposed to Radiation Therapy

**Official Title:** Pilot Study to Evaluate Esomeprazole (Nexium) in Treating Gastro-esophageal Reflux in Patients With Head and Neck Cancer With Prior External Beam Radiation Therapy: a Randomized, Prospective, Placebo-controlled, Double-blind Study.

#### Organization Study ID Info
**ID:** 200308067
#### Organization
**Class:** OTHER
**Full Name:** University of Iowa
### Status Module
#### Completion Date
**Date:** 2008-02

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2017-12-14

**Type:** ACTUAL

**Last Update Submit Date:** 2017-12-12

**Overall Status:** TERMINATED

#### Primary Completion Date
**Date:** 2007-10

**Type:** ACTUAL

#### Start Date
**Date:** 2004-11

**Type:** ACTUAL

**Status Verified Date:** 2017-12

#### Study First Post Date
**Date:** 2005-09-22
**Type:** ESTIMATED
**Study First Submit Date:** 2005-09-16
**Study First Submit QC Date:** 2005-09-16
**Why Stopped:** Project canceled due to the implementation of IMRT, fewer patients reporting xerostomia.
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Douglas Trask

#### Responsible Party

**Investigator Affiliation:** University of Iowa

**Investigator Full Name:** Douglas Trask

**Investigator Title:** Principal Investigator

**Type:** SPONSOR_INVESTIGATOR

### Description Module

**Brief Summary:** The purpose of this research study is to measure acid reflux into the throat both before and after medical treatment in people who have had radiation therapy to their head and neck for the treatment of cancer. Many people who have received head and neck radiation therapy develop a dry mouth as a result of the radiation damage to their saliva glands. In addition to the discomfort associated with a dry mouth, the decrease in saliva may increase the severity of gastro-esophageal reflux disease (acid reflux). Acid reflux occurs when acid escapes from your stomach into your throat. You may not have any symptoms of acid reflux, but often it can cause symptoms of heartburn or chest discomfort.

Acid reflux can be treated once it is diagnosed. Treatment consists of dietary changes, behavioral alterations, and medication. Medications are available that decrease the amount of acid in your stomach. Diagnosis of acid reflux is made with a pH-probe to test for acid in your throat.

**Detailed Description:** The annual incidence of squamous cell carcinoma of the head and neck (SCCHN) is 40,000 cases per year in the US and 60,000 cases per year in Europe. Radiation therapy is employed in combination with chemotherapy in primary treatment or as adjuvant therapy for over half of patients with SSCHN.

A high incidence of pathologic laryngopharyngeal reflux and gastroesophageal reflux is observed in patients with head and neck cancer. When treatment for the cancer includes radiation therapy, an incidence of 90% has been reported \[2\]. Although the interplay between acid reflux and the development of head and neck cancer remains unclear, there is a strong argument that radiation therapy worsens the problem by muting the body's ability to neutralize acid.

Radiation therapy is extensively used in the treatment of squamous cell carcinoma of the head and neck. Radiation therapy works by exploiting a survival differential between malignant cells and normal cells. Simply stated, the malignant cells are more likely to die with radiation when compared to normal non-malignant cells. However, not all normal cells respond equally and some normal tissues have marked sensitivity to radiation damage. Salivary glands are one such radiosensitive tissue that is permanently destroyed with external-beam radiotherapy.

Damage to salivary tissues by radiation decreases their ability to excrete saliva. This is supported by Olmos et al, who used salivary scintigraphy on both irradiated and non-irradiated patients and found that 84% of those irradiated had total or partial disturbance in both baseline and stimulated function. Of those treated with greater than 4500cGy, salivary excretion was almost invariably impaired. Xerostomia is the term for the dry mouth, which can result from this loss.

In addition to the volume of the saliva, the contents of the saliva are also important. Helm et al. "...evaluated the properties of human saliva relevant to its potential contribution to esophageal acid clearance." By measuring the capacity for acid neutralization and plotting titration curves, they identified that saliva and especially its bicarbonate content play an important role in neutralization of esophageal acid in both resting and lozenge-stimulated states.

As saliva plays an active role in the neutralization of esophageal acid and its clearance from the esophagus, loss of saliva is predicted to increase the severity and incidence of reflux as the protective effect of saliva's ability to clear and neutralize acid reflux is diminished. Korsten et al., assessed the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis and reported markedly impaired clearance of acid from the esophagus and abnormal 24-hour intra-esophageal pH studies from a cohort of male patients with xerostomia.

Medications are available to increase salivary flow but these are often minimally effective and poorly tolerated. Decreasing stomach acid production is an alternative method of mitigating the effect of GERD in these patients.

Esomeprazole has been proven beneficial in the treatment of gastroesophageal reflux disease and is anticipated to be beneficial in treating SCCHN patients treated with external-beam radiation therapy.

### Conditions Module

**Conditions:**

- Gastro-esophageal Reflux

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** DOUBLE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 40

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

### Interventions

#### Intervention 1

**Name:** Esomeprazole (Nexium)

**Type:** DRUG

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Signed informed consent
2. History of head and neck cancer
3. Radiation Therapy (external beam or IMRT)

   1. Must have received equal or greater than 5000 cGy cumulative dose
   2. Must have complaint of xerostomia
   3. Greater than three month interval since radiation treatment

Exclusion Criteria:

1. Subjects unable to tolerate pH-probe in past
2. Subjects currently on proton-pump inhibitor (PPI) or H-2 receptor antagonist therapy
3. Prior history of esophago-gastric surgery
4. Symptoms of gastrointestinal bleeding (melena, hematemesis)
5. Known hepatic cirrhosis or esophageal varices
6. Prior esophageal perforation
7. Pregnant, nursing or not likely to be using adequate contraceptive measures
8. Subjects not predicted to survive duration of study
9. Subjects with allergies or sensitivities to proton-pump inhibitors
10. Psychological, familial, sociological or geographical conditions which do not permit Study follow-up and compliance with study protocol
11. Subjects predicted to undergo surgery, chemotherapy or radiation therapy for head and neck cancer during the course of study

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Iowa City

**Country:** United States

**Facility:** University of Iowa Department of Otolaryngology

**State:** Iowa

**Zip:** 52242

#### Overall Officials

**Official 1:**

**Affiliation:** University of Iowa

**Name:** Douglas K trask, MD. Ph.D.

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000015154

- Term: Esophageal Motility Disorders

- ID: D000003680

- Term: Deglutition Disorders

- ID: D000004935

- Term: Esophageal Diseases

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000004941

- Term: Esophagitis

- ID: D000005759

- Term: Gastroenteritis

- ID: D000010437

- Term: Peptic Ulcer

- ID: D000004378

- Term: Duodenal Diseases

- ID: D000007410

- Term: Intestinal Diseases

- ID: D000013272

- Term: Stomach Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: BC09

- Name: Ear, Nose, and Throat Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M9348

- Name: Head and Neck Neoplasms

- Relevance: HIGH

- As Found: Head and Neck Cancer

- ID: M8880

- Name: Gastroesophageal Reflux

- Relevance: HIGH

- As Found: Gastro Esophageal Reflux

- ID: M8091

- Name: Esophagitis

- Relevance: LOW

- As Found: Unknown

- ID: M8092

- Name: Esophagitis, Peptic

- Relevance: HIGH

- As Found: Gastro Esophageal Reflux

- ID: M17874

- Name: Esophageal Motility Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M17875

- Name: Esophageal Spasm, Diffuse

- Relevance: LOW

- As Found: Unknown

- ID: M6882

- Name: Deglutition Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M8085

- Name: Esophageal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8875

- Name: Gastroenteritis

- Relevance: LOW

- As Found: Unknown

- ID: M17206

- Name: Ulcer

- Relevance: LOW

- As Found: Unknown

- ID: M13348

- Name: Peptic Ulcer

- Relevance: LOW

- As Found: Unknown

- ID: M7552

- Name: Duodenal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10444

- Name: Intestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M16062

- Name: Stomach Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006258

- Term: Head and Neck Neoplasms

- ID: D000005764

- Term: Gastroesophageal Reflux

- ID: D000004942

- Term: Esophagitis, Peptic

### Intervention Browse Module - Ancestors

- ID: D000000897

- Term: Anti-Ulcer Agents

- ID: D000005765

- Term: Gastrointestinal Agents

- ID: D000054328

- Term: Proton Pump Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: Gast

- Name: Gastrointestinal Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M30204

- Name: Esomeprazole

- Relevance: HIGH

- As Found: Risk of

- ID: M4188

- Name: Antacids

- Relevance: LOW

- As Found: Unknown

- ID: M4219

- Name: Anti-Ulcer Agents

- Relevance: LOW

- As Found: Unknown

- ID: M8881

- Name: Gastrointestinal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M27630

- Name: Proton Pump Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000064098

- Term: Esomeprazole

### Misc Info Module

- Version Holder: 2024-05-24
