A New Method for Determining Gastric Acid Output Using a Wireless Capsule

Acid related disorders are numerous and often require chronic treatment and maintenance. Many
of these diseases are without symptoms and therefore difficult to diagnose and treat. Gastric
analysis is the quantitative measurement of gastric acid output and is a critical tool for
the diagnosis of acid related disorders and the ongoing assessment of therapy response. At
present gastric analysis requires a technically difficult procedure, using gastric aspiration
through a nasogastric tube, that is costly, invasive, and uncomfortable for patients.
Recently there is introduction of the SmartPill, which is a disposable pill that measures pH,
temperature, and pressure throughout the GI tract. We propose a pilot study to validate a new
method of gastric analysis with the ingestion of the SmartPill with a meal of a known
buffering capacity to measure both the acidity and quantity of acid output in the stomach. We
will validate this method by comparing it to the accepted gastric aspiration method under
maximally stimulated conditions. We will study healthy volunteers for the validation phase
and then study patients with known acid related disorders to assess its usefulness in
patients. Interested subjects will report to the NIH outpatient gastrointestinal clinic for
evaluation to be followed by a 3 day in-patient admission and 2 subsequent clinic visits.
Subjects will have gastric analysis of basal, meal stimulated, and pharmacologically
stimulated rates with both the conventional and study methods. Outcomes will include a
quantitative measurement of gastric acid output in unit time, normal meal stimulated acid
output values in healthy volunteers and patients with acid related disorders, and the
assessment of acid suppression in patients treated with a variety of anti-secretory
medications.

- CURRENTLY ONLY RECRUITING Patients with Zollinger Ellison Syndrome and Hypersecretion
AND Patients with Refractory GERD, Peptic ulcer disease, Idiopathic Gastric
Hypersecretion

Phase II, Use in Patients with Zollinger Ellison Syndrome and Hypersecretion

INCLUSION:

- Zollinger-Ellison syndrome (ZES) as diagnosed by one of the following criteria:
histologic confirmation of gastrinoma, positive provocative testing with secretin (an
increase of >200 pg/mL postinjection), gastric acid hypersecretion (BAO > 15) in the
presence of hypergastrinemia (fasting serum gastrin > 99)

- Multiple endocrine neoplasia type-I (MEN1) with suspicion of ZES (hypergastrinemia)
undergoing evaluation. MEN-I with ZES

- Hypergastrinemia (serum gastrin > 99)

Patients must meet at least 1 of the above inclusion criteria and the following:

- Ages equal to or greater than 18 years

- Male, females, all ethnicities

EXCLUSION:

- History of gastric surgery (gastrectomy, pyloroplasty)

- Use of bowel motility medications such as, but not limited to, Reglan, Immodium, and
Lomotil

- Contraindication to SmartPill: history of gastric bezoar, disorders of swallowing,
suspected strictures, fistulas, or physiological GI obstruction, GI surgery within the
past three months, severe dysphagia to food or pills, Crohn s Disease or
diverticulitis, a subject who uses an implanted or portable electro-mechanical medical
device such as a cardiac pacemaker or infusion pump

- Pregnancy and breastfeeding. Females of childbearing potential must be on an
acceptable means of birth control and no intercourse in 2 weeks prior to study
enrollment.

- Lactose intolerance or inability to drink standard meal of Ensure Plus

- Estabished diagnosis of gastroparesis

- Significant systemic or major illnesses including, but not limited to, stroke,
congestive heart failure, renal failure (creatinine clearance < 50 ml/min), organ
transplantation, angina pectoris, active malignancy, and autonomic neuropathy

- Unstable psychiatric conditions, untreated or uncontrolled depression or generalized
anxiety disorder, substance abuse within the past year, in order to prevent feeling of
being uncomfortable or to prevent lack of follow-up

- Use of not-steroidal anti-inflammatory drugs for 2 weeks prior to study enrollment

Phase IIIA, Use in Patients with Refractory GERD, Peptic ulcer disease, Idiopathic Gastric
Hypersecretion

INCLUSION:

- Gastric acid hypersecretion (BAO>15 mEq/hr)

- Conditions with gastric acid hypersecretion including, but not limited to, patients
with systemic mastocytosis (SM)

- Refractory GERD (patients with persistant symptoms despite being on standard medical
therapy), PUD, and suspected idiopathic gastric hypersecretion

Patients must meet at least 1 of the above inclusion criteria and the following:

- Ages equal to or greater than 18 years

- Male, females, all ethnicities

EXCLUSION:

- History of gastric surgery (gastrectomy, pyloroplasty).

- Use of bowel motility medications such as, but not limited to, Reglan, Immodium, and
Lomotil

- Contraindication to SmartPill: history of gastric bezoar, disorders of swallowing,
suspected strictures, fistulas, or physiological GI obstruction, GI surgery within the
past three months, severe dysphagia to food or pills, Crohn s Disease or
diverticulitis, a subject who uses an implanted or portable electro-mechanical medical
device such as a cardiac pacemaker or infusion pump

- Pregnancy and breastfeeding. Females of childbearing potential must be on an
acceptable means of birth control and no intercourse in 2 weeks prior to study
enrollment.

- Lactose intolerance or inability to drink standard meal of Ensure Plus

- Established diagnosis of gastroparesis

- Significant systemic or major illnesses including, but not limited to, stroke,
congestive heart failure, renal failure (creatinine clearance < 50 ml/min), organ
transplantation, angina pectoris, active malignancy, and autonomic neuropathy

- Unstable psychiatric conditions, untreated or uncontrolled depression or generalized
anxiety disorders, substance abuse within the past year, in order to prevent feeling
of being uncomfortable or to prevent lack of follow-up. Use of non-steroidal
anti-inflammatory drugs for 2 weeks prior to study enrollment.

Phase IIIB, Use in Patients with Medication-Controlled: GERD, Peptic ulcer disease,
Idiopathic Gastric Hypersecretion

INCLUSION:

-Medication-controlled (patients whose symptoms resolve with medication):GERD, PUD, and
suspected idiopathic gastric hypersecretion

Patients must meet the above inclusion criteria and the following

- Ages equal to or greater than 18 years

- Male, females, all ethnicities

EXCLUSION:

- Refractory to medication: GERD (patients with persistant symptoms despite being on
standard medical therapy), PUD, and suspected idiopathic gastric hypersecretion

- History of gastric surgery (gastrectomy, pyloroplasty).

- Use of bowel motility medications such as, but not limited to, Reglan, Immodium, and
Lomotil

- Contraindication to SmartPill: history of gastric bezoar, disorders of swallowing,
suspected strictures, fistulas, or physiological GI obstruction, GI surgery within the
past three months, severe dysphagia to food or pills, Crohn s Disease or
diverticulitis, a subject who uses an implanted or portable electro-mechanical medical
device such as a cardiac pacemaker or infusion pump

- Pregnancy and breastfeeding. Females of childbearing potential must be on an
acceptable means of birth control and no intercourse in 2 weeks prior to study
enrollment.

- Lactose intolerance or inability to drink standard meal of Ensure Plus

- Established diagnosis of gastroparesis

- Significant systemic or major illnesses including, but not limited to, stroke,
congestive heart failure, renal failure (creatinine clearance < 50 ml/min), organ
transplantation, angina pectoris, active malignancy, and autonomic neuropathy

- Unstable psychiatric conditions, untreated or uncontrolled depression or genralized
anxiety disorders, substance abuse within the past year, in order to prevent feeling
of being uncomfortable or to prevent lack of follow-up

- Use of non-steroidal anti-inflammatory drugs for 2 weeks prior to study enrollment

RECRUITMENT IS CLOSED FOR Phase IA/IB, Validation and Establishment of Nomogram in Healthy
Volunteers

PHASE IA/IB INCLUSION:

- Healthy volunteers

- Ages 18-60

- Males, females, all ethnicities

PHASE IA/IB EXCLUSION:

- History of gastric or bowel surgery

- Use of bowel motility medications such as, but not limited to, Reglan, Immodium, and
Lomotil

- Use of antacid, antisecretory, and anticholinergic medications such as, but not
limited to, proton pump inhibitors and histamine 2 receptor antagonists

- Use of non-steroidal anti-inflammatory drugs for 2 weeks prior to study enrollment

- Hypersecretory and hyposecretory related conditions including, but not limited to,
pernicious anemia, atrophic gastritis, and Zollinger-Ellison syndrome

- Contraindication to NGT: deviated septum, history of transphenoidal surgery, chronic
sinusitis, severe facial trauma (cribriform plate disruption, sustained head trauma,
maxillofacial injury, or anterior fossa skull fracture), esophageal stricture,
esophageal varices, altered mental status, and impaired airway

- Contraindication to scintigraphy: allergy to sulfa-colloid

- Contraindication to pentagastrin: allergy to pentagastrin, active gastrointestinal
bleeding, active peptic ulcer disease, active gallbladder and liver disease,
pancreatitis, and bowel obstruction

- Contraindication to SmartPill: history of gastric bezoar, disorders of swallowing,
suspected strictures, fistulas, or physiological GI obstruction, GI surgery within the
past three months, severe dysphagia to food or pills, Crohns disease or
diverticulosis, and implanted or portable electro-mechanical medical device such as a
cardiac pacemaker or infusion pump

- Pregnancy and breastfeeding. Females of childbearing potential must be on an
acceptable means of birth control and no intercourse in 2 weeks prior to study
enrollment.

- Lactose intolerance or inability to drink standard meal of Ensure Plus

- Helicobacter pylori infection

- Gastroparesis

- History of gastroesophageal reflux disease, peptic ulcer disease, irritable bowel
syndrome, or inflammatory bowel disease

- Significant systemic or major illnesses including, but not limited to, stroke,
cardiovascular disease, hypertension, congestive heart failure, renal failure
(creatinine clearance < 50 ml/min), organ transplantation, angina pectoris, active
malignancy, diabetes, or autonomic neuropathy

- Unstable psychiatric conditions, depression, generalized anxiety disorder, or
substance abuse within the past year, in order to prevent feeling of being
uncomfortable or to prevent lack of follow-up