Official Title: “The Effect Of Pantoprazole 40 mg Once Daily Versus Placebo On The Power Spectral Analysis Of The Sleep Electroencephalogram Of Patients With Gastroesophageal Reflux Disease”

The purpose of this research study is to determine if treatment with pantoprazole 40 mg daily versus a placebo improves sleep quality in patients with gastroesophageal reflux disease (GERD). Another purpose is to determine if treatment with pantoprazole 40 mg once daily versus a placebo improves sleep outcomes in patients with gastroesophageal reflux disease using spectral analysis of sleep electroencephalogram (EEG).

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2010

It appears that the presence of intraesophageal stimuli alone may not be sufficient to elicit symptoms of heartburn. Most acid reflux events (>80%-90%) do not reach conscious level and thus are not perceived.[3] It is yet to be determined what factors enhance our perception of esophageal stimuli and may help to elevate them to the conscious level. In recent years, central and peripheral factors that may enhance our perception of intraesophageal stimuli have been evaluated. Intraduodenal fat infusion was shown to enhance perception of intraesophageal acid in patients with GERD.[4] This study suggested that fat is an important modulator of postprandial GERD symptoms. Central factors, such as stress and psychological comorbidity, also appear to have an important role in symptom generation in patients with GERD, regardless if esophageal inflammation is present or absent.[5-8] Thus, by modulating brain-gut interactions, perception of pathological and probably physiological events in the esophagus of patients with GERD may be altered.

Poor sleep is a central factor that may enhance perception of intraesophageal stimuli and thus elevate them to the conscious level. Several studies have demonstrated that patients with fibromyalgia or irritable bowel syndrome report increased symptoms due to sleep abnormalities.[9, 10] Similar reports in patients with GERD are not available. A subset of patients with GERD experience nocturnal heartburn that may awaken them during the night. In others, despite lack of nocturnal symptoms, sleep abnormalities may occur due to acid reflux events. In both cases, GERD leads to poor sleep, and that in turn may enhance perception of intraesophageal stimuli, leading to reports of increased frequency and severity of perceived GERD symptoms. Thus, poor sleep may be a crucial factor in symptom generation and exacerbation of patients with GERD.

Recently, we have used a novel technique, power spectral analysis of the sleep electroencephalogram (EEG), to assess patients with heartburn and erosive esophagitis and those with heartburn but without erosive esophagitis.[11] We were able to show that among heartburn patients with GERD, EEG spectral power during sleep is shifted towards higher frequencies as compared to heartburn patients without GERD despite similar sleep architecture.

Several recent therapeutic trials in GERD patients have failed to demonstrate improvement in polysomnographic studies despite improvement in GERD-related symptoms and subjective reports of sleep quality.[12] Spectral analysis of the sleep EEG might be a more sensitive tool than polysomnographic study in assessing objective improvement of sleep in patients receiving antireflux treatment.

In summary, sleep disturbances in patients with GERD are poorly recognized and rarely elicited during clinic visits despite their significant impact on patients' quality of life and probably perception of disease severity. Several studies have demonstrated improvement of subjective reports of sleep quality in patients with GERD receiving antireflux treatment.

However, the effect of potent antireflux therapy on objective sleep parameters has yet to be demonstrated.

Intervention(s) in this Clinical Trial

• Drug: Pantoprazole
  • 40 mg once daily for 4 weeks

Primary Measures

• symptom control after 4 weeks of treatment.
  • Time Frame: April 2008 to July 2010
    Safety Issue?: Yes

Inclusion Criteria:

• 18 to 80 yrs of age
• 2 to 3 episodes of GERD/week
• erosive esophagitis or abnormal 24 hr pH
• able to read and understand, complete questionnaires

Exclusion Criteria:

• barrett's esophagus or peptic stricture on endoscopy
• normal EGD and normal 24 hour pH
• previous upper GI surgery
• comorbidity (cardiovascular, respiratory, renal, hepatic)
• use of narcotics or pain medication on regular basis
• insomnia, shift work sleep disorder, sleep apnea, restless leg syndrome
• diabetes, scleroderma or neuromuscular disorders

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Southern Arizona VA Health Care System

Overall Clinical Trial Officials and Contacts

Ronnie Fass, MD Principal Investigator Southern VA Health Care System  

Overall Contact: Marcia R Willis, B.A. 520-792-1450 marcia.willis@va.gov

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00674245

Study ID Number: 08-0001-01 & R&D#00-77

ClinicalTrials.gov Identifier: NCT00674245

Health Authority: United States: Food and Drug Administration