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Buspirone for Early Satiety and Symptoms of Gastroparesis (BESST)

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ClinicalTrials.gov Identifier: NCT03587142
Recruitment Status : Not yet recruiting
First Posted : July 16, 2018
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary:
This study evaluates whether the study medication, buspirone, an antianxiety drug, improves the symptoms of gastroparesis in patients with gastroparesis symptoms and at least moderately severe symptoms of fullness and/or inability to eat a full meal. Half the patients will receive buspirone and half the patients will receive a placebo.

Condition or disease Intervention/treatment Phase
Gastroparesis Drug: Buspirone Drug: Placebo Phase 2

Detailed Description:
This is a multi-center, randomized, double-masked, placebo-controlled, parallel treatment groups phase 2 trial to determine the effect of buspirone, a 5-hydroxytryptamine (5-HT) 1a receptor agonist, on early satiety and postprandial fullness in participants with symptoms of gastroparesis and with at least moderately severe symptoms of early satiety and/or postprandial fullness. After enrollment, participants aged 18-75 years will be treated with buspirone (10 mg three times per day) or a matching placebo for 4 weeks, followed by a 2-week post-treatment washout period. The primary outcome for the study is 4-week change (week 4 minus baseline) in the 4-item postprandial fullness/early satiety subscore (higher scores indicate worse symptoms) from the Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) Gastroparesis Cardinal Symptom Index (GCSI). We hypothesize that buspirone treatment will improve symptoms of postprandial fullness/early satiety compared to treatment with placebo, as indicated by a lower (smaller, more negative) 4-week change in the postprandial fullness/early satiety subscore in the buspirone arm compared to the placebo arm; change for a participant will be calculated as subscore at 4-weeks minus subscore at baseline.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: BESST is a multi-center, randomized, placebo-controlled, double-masked, parallel treatment groups phase 2 trial with half the participants receiving the study drug, buspirone, and half receiving the placebo.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

Participants, all clinic staff and the investigators will be masked as to whether the participant is receiving buspirone or the placebo.

The study drug will be over encapsulated in a size 0 gelatin capsule with partial filler to be identical to the placebo capsule, which contains only filler.

The random treatment assignment will consist of a numbered study drug bottle; each bottle number will be unique and each participant will be assigned a specific bottle number, which is labelled: "Buspirone or placebo 10 mg." with directions.

The randomization scheme will assign participants in randomly permuted blocks of assignments stratified by clinical center. The randomization plan will be prepared and administered centrally via a secure web application by the Scientific Data Research Center.

Primary Purpose: Treatment
Official Title: Buspirone for Early Satiety and Symptoms of Gastroparesis: A Multicenter, Randomized, Placebo-Controlled, Double-Masked Trial (BESST)
Estimated Study Start Date : December 28, 2018
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Buspirone
Buspirone HCl 10 mg capsule orally three times daily, 30 minutes before each meal, for 4-weeks
Drug: Buspirone
Buspirone tablet
Other Names:
  • Buspar
  • buspirone hydrochloride (HCl)
  • Buspar Dividose
  • Vanspar

Placebo Comparator: Placebo
Placebo capsule orally three times daily, 30 minutes before each meal, for 4-weeks; manufactured to look identical to buspirone capsule
Drug: Placebo
"Sugar" pill manufactured to mimic buspirone 10 mg tablet
Other Name: Placebo (for buspirone)




Primary Outcome Measures :
  1. 4-Week Change in the Postprandial Fullness and Early Satiety Symptoms Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported postprandial fullness/early satiety subscore, which is computed as the average of 4 scores for 4-items on the Gastroparesis Cardinal Symptom Index (GCSI) survey: stomach fullness, inability to finish a normal-sized meal, feeling excessively full after meals, and loss of appetite. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore.


Secondary Outcome Measures :
  1. 4-Week Change in Total Overall GCSI Symptom Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported total GCSI score, which is computed as the average of the 3 subscores on the GCSI survey: 3-item postprandial fullness/early satiety subscore, the nausea/vomiting subscore (average of 3-items: nausea, retching, vomiting), and bloating subscore (average of 2-items: bloating, stomach visibly larger). Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the total score ranges from 0 to 5. the change is computed as the total score at 4-weeks minus the baseline total score.

  2. 4-Week Change in Nausea, Vomiting and Retching Symptoms Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported nausea/vomiting subscore, which is computed as the average of 3 scores for 3-items on the GCSI survey: nausea, retching, vomiting. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore.

  3. 4-Week Change in Bloating and Stomach Distention Symptoms Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported bloating subscore, which is computed as the average of 2 scores for 2-items on the GCSI survey: bloating, stomach visibly larger. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore.

  4. 4-Week Change in Upper Abdominal Pain and Discomfort Symptoms Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported upper abdominal pain subscore, which is computed as the average of 2 scores for 2-items on the PAGI-SYM survey: upper abdominal pain, upper abdominal discomfort. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore.

  5. 4-Week Change in Gastroesophageal (GERD) Symptoms Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported GERD subscore, which is computed as the average of 7 scores for 7-items on the Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) survey: heartburn during the day, heartburn when lying down, feeling of discomfort inside chest during the day, feeling of discomfort inside chest during sleep, regurgitation or reflux during the day, regurgitation when lying down, bitter, acid or sour taste in mouth. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore.

  6. 4-Week Change in Nausea Symptom Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using self-reported assessment of nausea severity in the prior 2-weeks using the GCSI survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score.

  7. 4-Week Change in Vomiting Symptom Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using self-reported assessment of vomiting severity in the prior 2-weeks using the GCSI survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score.

  8. 4-Week Change in Stomach Fullness Symptom Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using self-reported assessment of stomach fullness severity in the prior 2-weeks using the GCSI survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score.

  9. 4-Week Change in Inability to Finish a Normal-sized Meal Symptom Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using self-reported assessment of inability to finish a normal-sized meal severity in the prior 2-weeks using the GCSI survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score.

  10. 4-Week Change in Excessive Fullness Symptom Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using self-reported assessment of feeling excessively full after meals severity in the prior 2-weeks using the GCSI survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score.

  11. 4-Week Change in Loss of Appetite Symptom Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using self-reported assessment of loss of appetite severity in the prior 2-weeks using the GCSI survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score.

  12. 4-Week Change in Bloating Symptom Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using self-reported assessment of bloating severity in the prior 2-weeks using the GCSI survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score.

  13. 4-Week Change in Upper Abdominal Pain Symptom Severity [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using self-reported assessment of upper abdominal pain severity in the prior 2-weeks using the GCSI survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score.

  14. 4-Week Change in Gastrointestinal Symptoms Rating Scale (GSRS) Global Score [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported GSRS total score which is computed as the mean of the 15 item scores on the GSRS survey. Each item is scored from 1 (no discomfort) to 7 (very severe discomfort) of the symptom in the past week. The change is computed as the score at 4-weeks minus the baseline score.

  15. 4-Week Change in Participant's Rating of Symptom Relief [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the participant-rated Clinical Patient Grading Assessment Scale (CPGAS) score which is scored from -3 (very considerably worse) to 3 (completely better) in the past week compared to the way the participant usually feels. The change is computed as the score at 4-weeks minus the baseline score.

  16. 4-Week Change Overall Quality of Health due to Gastroparesis Issues [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL) total score which comprises 30 items scored from 0 (none of the time) to 5 (all of the time) the participant's QOL has been affected by their gastrointestinal issues in the prior two weeks. The total score is the mean of the 5 subscale scores and ranges from 0 (lowest QOL) to 5 (highest QOL) in past 2-weeks. The change is computed as the score at 4-weeks minus the baseline score.

  17. 4-Week Change in Depression [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported Hospital Anxiety and Depression Scale (HADS) depression subscore, calculated as the sum of 7 items, each scored from 0 (not at all) to 3 (most of the time). The change is computed as the subscore at 4-weeks minus the baseline subscore.

  18. 4-Week Change in Anxiety [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported Hospital Anxiety and Depression Scale (HADS) anxiety subscore, calculated as the sum of 7-items, each scored from 0 (not at all) to 3 (most of the time). The change is computed as the subscore at 4-weeks minus the baseline subscore.

  19. 4-Week Change in Severity of Somatic Symptoms [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported Patient Health Questionnaire 15 Somatic Symptom Severity Scale (PHQ-15) total somatization score, calculated as the sum of 15-items, each scored from 0 (not bothered at all) to 3 (bothered a lot) by somatic symptoms in the prior 4-weeks. The change is computed as the score at 4-weeks minus the baseline score.

  20. 4-Week Change in Overall Mental Quality of Life (QOL) [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported 36-item Short Form Health Survey (SF-36v2) mental health QOL component score. The score ranges from 0 (poorest) to 100 (highest) QOL. The change is computed as the score at 4-weeks minus the baseline score.

  21. 4-Week Change in Overall Physical Quality of Life (QOL) [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the self-reported 36-item Short Form Health Survey (SF-36v2) physical health QOL component score. The score ranges from 0 (poorest) to 100 (highest) QOL. The change is computed as the score at 4-weeks minus the baseline score.

  22. 4-Week Change in Gastric Retention [ Time Frame: baseline and 4-weeks ]
    The outcome is assessed using the percent of gastric retention at 4-hours from the Gastric Emptying Scintigraphy (GES) test. The change is computed as the percent retention at 4-weeks minus the baseline percent retention.


Other Outcome Measures:
  1. 4-Week Change in Weight [ Time Frame: baseline and 4-weeks ]
    This safety outcome is computed by subtracting the weight (kg) at baseline from the weight (kg) at 4-weeks

  2. 4-Week Cardiac Rhythm [ Time Frame: 4-weeks ]
    This safety outcome is computed from the results of an electrocardiogram (ECG) at 4-weeks.

  3. 4-Week Change in aspartate aminotransferase (ALT) [ Time Frame: baseline and 4-weeks ]
    This safety outcome is computed by subtracting the baseline level of ALT (U/L) from the 4-week level.

  4. 4-Week Change in Creatinine [ Time Frame: baseline and 4-weeks ]
    This safety outcome is computed by subtracting the baseline level of creatinine (mg/dL) from the 4-week level.

  5. 4-Week Change in Fasting Glucose [ Time Frame: baseline and 4-weeks ]
    This safety outcome is computed by subtracting the baseline level of glucose (mg/dL) from the 4-week level.

  6. Assessment of Symptom Side Effects over 4-Weeks [ Time Frame: over 4-weeks ]
    This safety outcome is the frequency over the 4-weeks of the study of symptom side effects as reported on the 9 questions of the Symptom Side Effects survey.

  7. Assessment of Adverse Events over 4-Weeks [ Time Frame: over 4-weeks ]
    This safety outcome is the frequency over the 4-weeks of the study of all reported adverse events.

  8. Assessment of the Severity of Adverse Events over 4-Weeks [ Time Frame: over 4-weeks ]
    This safety outcome is the frequency over the 4-weeks of the study of all reported adverse events' severity grade as classified by the NCI's Common Terminology Criteria for Adverse Events (CTCAE v5.0).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 to 75 years of age at initial screening interview
  • Symptoms compatible with gastroparesis or other functional gastric disorder for at least 3 months (does not have to be contiguous) prior to initial screening interview
  • Diagnosis of either diabetic or idiopathic gastroparesis
  • Delayed or normal gastric emptying retention on screening 4-hour Gastric Emptying Scintigraphy test
  • Symptoms of gastroparesis measured by the 9-item PAGI-SYM Gastroparesis Cardinal Symptom Index (GCSI) total score > 2.0 at enrollment
  • Symptomatic with postprandial fullness/early satiety severity at enrollment using the PAGI-SYM GCSI post-prandial fullness/early satiety subscore ≥ 3
  • Upper endoscopy or upper GI series without ulcers or mass lesions in the 2 years prior to enrollment

Exclusion Criteria:

  • Post-surgical gastroparesis, including prior pyloromyotomy, pyloric resection, vagotomy, bariatric surgery or post-Nissen fundoplication
  • Another active disorder which could explain symptoms in the opinion of the investigator
  • Concurrent use of opiate narcotic analgesics more than 3 days per week
  • Significant hepatic injury as defined by alanine aminotransferase (ALT) elevation of greater than twice the Upper Limit of Normal (ULN) or a Child-Pugh score of 10 or greater
  • Significant renal impairment as defined by serum creatinine > 3.0
  • Uncontrolled diabetes defined as HbA1c (%) of 10% or more within 60 days of enrollment
  • Allergy to buspirone
  • Concurrent or prior use (within 30 days) of monoamine oxidase (MAO) inhibitors
  • Concurrent or prior use (within 30 days) of benzodiazepines
  • Concurrent or prior use (within 30 days) of buspirone, warfarin, haloperidol, and drugs to treat seizures (e.g., phenytoin and carbamazepine)
  • Women breast feeding or known to be pregnant
  • Any other condition, which in the opinion of the investigator would impede compliance or hinder completion of the study
  • Failure to give informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03587142


Contacts
Contact: SDRC Principal Investigator James /Tonascia, PhD 410-955-3704 jtonasc1@jhu.edu
Contact: Katherine P Yates, ScM 443-287-0082 kyates1@jhu.edu

Locations
United States, Kentucky
University of Louisville Not yet recruiting
Louisville, Kentucky, United States, 40202
Principal Investigator: Thomas Abell, MD         
United States, Maryland
Johns Hopkins Hospital Not yet recruiting
Baltimore, Maryland, United States, 21287
Principal Investigator: Pankaj J Pasricha, MD         
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Braden Kuo, MD         
United States, North Carolina
Wake Forest University Health Sciences Not yet recruiting
Winston-Salem, North Carolina, United States, 27157
Principal Investigator: Kenneth Koch, MD         
United States, Pennsylvania
Temple University Not yet recruiting
Philadelphia, Pennsylvania, United States, 19140
Principal Investigator: Henry P Parkman, MD         
United States, Texas
Texas Tech University Health Science Center Not yet recruiting
El Paso, Texas, United States, 79905
Principal Investigator: Richard W McCallum, MD         
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Henry P Parkman, MD Temple University Hospital, Philadelphia, PA
Study Chair: Pankaj J Pasricha, MD Johns Hopkins Hospital, Baltimore, MD

Additional Information:
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT03587142     History of Changes
Other Study ID Numbers: 10- GpCRC3-BESST
U01DK073983 ( U.S. NIH Grant/Contract )
U01DK112193 ( U.S. NIH Grant/Contract )
U01DK073975 ( U.S. NIH Grant/Contract )
U01DK074035 ( U.S. NIH Grant/Contract )
U01DK074007 ( U.S. NIH Grant/Contract )
U01DK073974 ( U.S. NIH Grant/Contract )
U24DK074008 ( U.S. NIH Grant/Contract )
First Posted: July 16, 2018    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The study will comply with the NIH Data Sharing Policy. The data will be first de-identified so that no individual participant identifiers will be included in the dataset (no names, addresses, dates, comments, etc). If a characteristic is an extreme value for this population, then those values will be categorized into one frequency group. If a CSR has multiple versions, then all data will be recoded into the format of the most current form version. A random unique identification number will be substituted for the unique BESST identification number. If a clinical item was obtained from surveys with restrictions due to licensing, then that data will be excluded. The data will be shared in 2 stages: the first will be the analytic datasets to produce the primary outcome paper. For this dataset, the documentation will include analytic code. The full dataset by CSR will be provided in the second stage.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: The analytic datasets to produce the primary result manuscript will be submitted within one year of publication of the primary result manuscript. The full clinical dataset for all Clinical Study Reports (CSRs) without proprietary restrictions will be submitted within 2 years of the primary result manuscript publication. This data will be available publicly indefinitely.
Access Criteria: An investigator interested in acquiring BESST study data should contact the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository at https://www.niddkrepository.org/search/study/ and apply to obtain the data required for their study.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
gastroparesis
early satiety
stomach
buspirone
5-HT 1a receptor agonist

Additional relevant MeSH terms:
Gastroparesis
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Paralysis
Neurologic Manifestations
Signs and Symptoms
Buspirone
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action