Clinical trial NCT01149369: Aprepitant for the Relief of Nausea in Patients With Chronic Nausea and Vomiting of Presumed Gastric Origin Trial
Official title: Aprepitant for the Relief of Nausea in Patients With Chronic Nausea and Vomiting of Presumed Gastric Origin: A Multicenter, Randomized, Double-Masked, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastroparesis
Keywords: gastroparesis
nausea
vomiting
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
First posted: 2010-06-23
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The principal objective of this multicenter, randomized, placebo-controlled trial is to evaluate whether 4 weeks of treatment with aprepitant will improve nausea as compared with placebo in patients with symptoms of chronic nausea and vomiting of presumed gastric origin.

Detailed description: APRON is a multicenter, randomized, double-masked, placebo controlled trial of 4 weeks of treatment with aprepitant or placebo for patients with symptoms of gastroparesis and related disorders. Screening for eligibility and collection of baseline data will span up to 4 weeks after obtaining informed consent and registration. Eligible patients will consist of patients with symptoms of gastroparesis and will be randomized to either aprepitant (125 mg per day) or placebo for 4 weeks.

The symptoms will be measured with the Gastroparesis Cardinal Symptom Index Daily Diary (GCSIDD) for one week at baseline and for four weeks after randomization. In addition, the nausea symptom will be measured daily on a 0 to 100 mm visual analog scale (VAS) for one week at baseline and daily for four weeks after randomization. There will be a 2 week washout period at the end of the treatment to ensure patient safety following the end of treatment.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older at registration
* Gastric emptying scintigraphy within 2 years of registration
* Normal upper endoscopy or upper GI series within 2 years of registration
* Symptoms of chronic nausea or vomiting compatible with gastroparesis or other functional gastric disorder for at least 6 months (does not have to be contiguous) prior to registration with Gastroparesis Cardinal Symptom Index (GCSI) score of greater than or equal to 21
* Significant nausea defined with a visual analog scale (VAS) score of greater than or equal to 25 mm on a 0 to 100 mm scale

Exclusion Criteria:

* Another active disorder which could explain symptoms in the opinion of the investigator
* Use of narcotics more than 3 days per week
* Significant hepatic injury as defined by significant alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations of greater than 2x the upper limit of normal (ULN) or a Child-Pugh score of 10 or greater
* Contraindications to aprepitant such as hypersensitivity or allergy
* Concurrent use of warfarin, pimozide, terfenadine, astemizole, or cisapride
* Pregnancy or nursing
* Any other condition, which in the opinion of the investigator would impede compliance or hinder the completion of the study
* Failure to give informed consent

Primary outcomes:
measure: Number of Participants With Improvement in Nausea
timeFrame: 4 weeks
Secondary outcomes:
measure: Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Nausea (Hours)
timeFrame: 4 weeks
measure: Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Vomiting (No. Episodes)
timeFrame: 4 weeks
measure: Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Retching (No. Episodes)
timeFrame: 4 weeks
measure: Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): GCSI Total Score
timeFrame: 4 weeks
measure: Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Nausea Severity
timeFrame: 4 weeks
measure: Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Vomiting Severity
timeFrame: 4 weeks
measure: Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Upper Abdominal Pain Severity
timeFrame: 4 weeks
measure: Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Excessive Fullness Severity
timeFrame: 4 weeks
measure: Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Early Satiety Severity
timeFrame: 4 weeks
measure: Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Bloating Severity
timeFrame: 4 weeks
measure: Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Overall Symptom Severity
timeFrame: 4 weeks
measure: Clinical Global Patient Impression Score (Patient-rated)
timeFrame: 4 weeks
measure: Liver Enzymes and Proteins: Alanine Aminotransferase (ALT)
timeFrame: 4 weeks
measure: Liver Enzymes and Proteins: Aspartate Aminotransferase (AST)
timeFrame: 4 weeks
measure: Liver Enzymes and Proteins: Total Protein
timeFrame: 4 weeks
measure: Hemoglobin A1c (HbA1c)
timeFrame: 4 weeks
measure: Glucose
timeFrame: 4 weeks
measure: Liver Enzymes and Proteins: Albumin
timeFrame: 4 weeks
measure: Hemoglobin
timeFrame: 4 weeks
measure: Hematocrit
timeFrame: 4 weeks
measure: White Blood Cell Count (WBC)
timeFrame: 4 weeks
measure: Red Blood Cell Count (RBC)
timeFrame: 4 weeks
measure: Platelet Count
timeFrame: 4 weeks
measure: Carbon Dioxide
timeFrame: 4 weeks
measure: Chloride
timeFrame: 4 weeks
measure: Sodium
timeFrame: 4 weeks
measure: Potassium
timeFrame: 4 weeks
measure: Calcium
timeFrame: 4 weeks
measure: Blood Urea Nitrogen (BUN)
timeFrame: 4 weeks
measure: Magnesium
timeFrame: 4 weeks
measure: Creatinine
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Gastroparesis Cardinal Symptom Index (GCSI) Score
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Nausea/Vomiting Severity Subscore
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Fullness/Early Satiety Subscore
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Bloating Subscore
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Upper Abdominal Pain Subscore
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: GERD Subscore
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Nausea Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Vomiting Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Retching Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Stomach Fullness Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Unable to Finish Meal Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Excessive Fullness Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Loss of Appetite Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Bloating Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Stomach Distention Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Upper Abdominal Pain Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Upper Abdominal Discomfort Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Lower Abdominal Pain Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Lower Abdominal Discomfort Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Heartburn During the Day Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Heartburn When Lying Down Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Chest Discomfort During the Day Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Chest Discomfort During Sleep Time Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Regurgitation During the Day Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Regurgitation When Lying Down Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity: Bitter Taste Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Constipation Severity
timeFrame: 4 weeks
measure: PAGI-SYM Severity Index: Diarrhea Severity
timeFrame: 4 weeks
measure: Gastrointestinal Symptom Rating Scale (GSRS): Total Score
timeFrame: 4 weeks
measure: Gastrointestinal Symptom Rating Scale (GSRS): Reflux Score
timeFrame: 4 weeks
measure: Gastrointestinal Symptom Rating Scale (GSRS): Abdominal Pain Score
timeFrame: 4 week
measure: Gastrointestinal Symptom Rating Scale (GSRS): Indigestion Score
timeFrame: 4 weeks
measure: Gastrointestinal Symptom Rating Scale (GSRS): Diarrhea Score
timeFrame: 4 weeks
measure: Gastrointestinal Symptom Rating Scale (GSRS): Constipation Score
timeFrame: 4 weeks
measure: Brief Pain Inventory: Severity Score
timeFrame: 4 weeks
measure: Brief Pain Inventory: Interference Score
timeFrame: 4 weeks
measure: Beck Depression Inventory (BDI) Score
timeFrame: 4 weeks
measure: State-Trait Anxiety Inventory (STAI): State Anxiety Score
timeFrame: 4 weeks
measure: State-Trait Anxiety Inventory (STAI): Trait Anxiety Score
timeFrame: 4 weeks
measure: Satiety Test, Volume Consumed
timeFrame: 4 weeks
measure: Electrogastrography (EGG): Bradygastria (1-<2.5 Cpm) at 4 Weeks, Baseline Measurement
timeFrame: 4 weeks
measure: Electrogastrography (EGG): Bradygastria (1-<2.5 Cpm) at 4 Weeks, 0-30 Post-satiety Measurement
timeFrame: 4 weeks
measure: Electrogastrography (EGG): Normogastria (2.5-<3.8 Cpm) at 4 Weeks, Baseline Measurement
timeFrame: 4 weeks
measure: Electrogastrography (EGG): Normogastria (2.5-<3.8 Cpm) at 4 Weeks, 0-30 Post-satiety Measurement
timeFrame: 4 weeks
measure: Electrogastrography (EGG): Tachygastria (3.8-10 Cpm) at 4 Weeks, Baseline Measurement
timeFrame: 4 weeks
measure: Electrogastrography (EGG): Tachygastria (3.8-10 Cpm) at 4 Weeks, 0-30 Post-satiety Measurement
timeFrame: 4 weeks
measure: Electrogastrography (EGG): Duodenal (>10-15 Cpm) at 4 Weeks, Baseline Measurement
timeFrame: 4 weeks
measure: Electrogastrography (EGG): Duodenal (>10-15 Cpm) at 4 Weeks, 0-30 Post-satiety Measurement
timeFrame: 4 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
Study officials:
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Frank Hamilton, MD, MPH
role: STUDY_DIRECTOR
References:
citation: Pasricha PJ, Yates KP, Sarosiek I, McCallum RW, Abell TL, Koch KL, Nguyen LAB, Snape WJ, Hasler WL, Clarke JO, Dhalla S, Stein EM, Lee LA, Miriel LA, Van Natta ML, Grover M, Farrugia G, Tonascia J, Hamilton FA, Parkman HP; NIDDK Gastroparesis Clinical Research Consortium (GpCRC). Aprepitant Has Mixed Effects on Nausea and Reduces Other Symptoms in Patients With Gastroparesis and Related Disorders. Gastroenterology. 2018 Jan;154(1):65-76.e11. doi: 10.1053/j.gastro.2017.08.033. Epub 2017 Oct 28.