Trial record 11 of 35 for:    Open Studies | "Gastroparesis"

A Pilot Study on the Efficacy and Safety of Olanzapine in Gastroparesis

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of Vermont
Sponsor:
Collaborator:
Massachusetts General Hospital
Information provided by (Responsible Party):
Allen Lee, University of Vermont
ClinicalTrials.gov Identifier:
NCT01625923
First received: June 18, 2012
Last updated: April 21, 2014
Last verified: April 2014
  Purpose

Gastroparesis is a disorder characterized by impaired gastric emptying in the absence of obstruction in the proximal GI tract. It is a common condition affecting up to 5 million persons in the United States alone. Despite this, metoclopramide is currently the only FDA approved medication for the treatment of gastroparesis. However, the evidence supporting metoclopramide in gastroparesis is fairly weak and was recently issued a black box warning because of potential irreversible side effects. There is clearly an urgent need for newer therapeutic options with better efficacy and tolerability. Olanzapine is a second generation anti-psychotic that is currently FDA approved for the treatment of schizophrenia and bipolar disorder. Because of actions at several receptors throughout the body, including dopamine and serotonin receptors, Olanzapine may provide anti-nausea and pro-motility effects in the stomach. Long-term use of olanzapine may also increase plasma levels of ghrelin. Ghrelin is a hormone produced by the gut that stimulates appetite and has also been shown to have beneficial effects on gastroparesis. The investigators hypothesize that olanzapine will be effective and safe in controlling symptoms as well as stimulate appetite and weight gain in gastroparesis. The investigators also hypothesize that olanzapine will stimulate gastric motility. Finally, the investigators hypothesize that olanzapine will modulate the secretion of ghrelin in gastroparesis. This pilot study may provide further information on the efficacy and safety of olanzapine in gastroparesis which could be utilized in a larger randomized, prospective study in the future.


Condition Intervention
Idiopathic Gastroparesis
Drug: Olanzapine

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study on the Efficacy and Safety of Olanzapine in Improving Symptoms and Gastric Motility in Gastroparesis

Resource links provided by NLM:


Further study details as provided by University of Vermont:

Primary Outcome Measures:
  • Number of subjects with adverse events [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Subjects will undergo regular testing of blood glucose, insulin, hemoglobin (Hgb) A1c, body mass index (BMI), liver enzymes, thyroid stimulating hormone (TSH), and prolactin levels during the study as well as after treatment completion to determine the safety of the medication. All adverse events will be compiled to investigate the tolerability of the medication.

  • Number of subjects with symptomatic improvement [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    The investigators will utilize the gastroparesis cardinal symptom index daily diary (GCSI-DD) and an appetite visual analog scale (VAS) to compare severity of symptoms before and after treatment with olanzapine.


Secondary Outcome Measures:
  • Number of subjects with improved gastric motility [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    The investigators aim to test gastric motility, including gastric emptying and antroduodenal contractility parameters, by wireless motility capsule (WMC) before and at the completion of the study to determine if olanzapine has any pro-motility effects in gastroparesis.

  • Number of subjects with altered ghrelin levels [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    The investigators seek to determine whether olanzapine promotes secretion of ghrelin in gastroparesis.


Estimated Enrollment: 20
Study Start Date: January 2013
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Olanzapine
An open-label pilot study of 20 consecutive subjects ages 18 - 65 with documented delayed gastric emptying within the past 2 years and history of nausea, vomiting, bloating, anorexia, early satiation, post-prandial fullness, and weight loss for at least 6 months without structural or organic cause will be enrolled.
Drug: Olanzapine
Subjects will initially start on olanzapine 2.5 mg per mouth daily. Subjects will return on days 7 and 14 to determine response to medication and medication dose can be increased to 5 mg and 10 mg, respectively, based on incomplete symptom response (mean change GCSI-DD < 0.5). The total dose of olanzapine will not exceed 10 mg daily during this study and subjects will continue on treatment for a total of 8 weeks.
Other Name: Zyprexa

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female between 18 and 65 years of age
  • Must have a > or = 6 month history of relevant symptoms of gastroparesis, (e.g., chronic post-prandial fullness, early satiety, postprandial nausea), patients will have a mean of the daily scores over a minimum of 7 days indicating > or = mild (2) and < or = severe (4) post-prandial fullness assessed using the GCSI-DD during the screening period prior to randomization
  • Documented abnormal gastric emptying within the past 2 years
  • Has gastroparesis at screening (gastric half-time of emptying > upper limit of normal as determined by wireless motility capsule)
  • BMI between 18 - 25 kg/m2
  • A female subject is eligible to participate if she is of non-childbearing potential or child-bearing potential and agrees to use one of the approved contraception methods. Female patients must agree to use contraception for at least 5 days following the last dose of study medication
  • Subject has never had a gastrectomy, nor major gastric surgical procedure or any evidence of bowel obstruction or strictures within the previous 12 months
  • Dosage of any concomitant medications has been stable for at least 3 weeks.
  • Estimated (or measured) glomerular filtration rate ≥ 30 mL/min
  • QTcB or QTcF < 450 msec or QTc < 480 msec in patients with Bundle Branch. Block based on single or average QTc value of triplicate values obtained over a brief recording period
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
  • AST and ALT < 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN; normal CBC, TSH, and prolactin levels

Exclusion Criteria:

  • History of diabetes mellitus or hyperglycemia
  • History of cardiovascular or cerebrovascular disease
  • History of hyperlipidemia
  • History of cardiac arrhythmia or long QT syndrome
  • History of seizure disorder
  • History of hyperprolactinemia
  • History of renal dysfunction
  • History of hepatic impairment
  • History of schizophrenia, bipolar disorder, or previous use of olanzapine
  • History of Parkinson's disease, dementia or severe cognitive impairment
  • History of GI surgery or placement of gastric pacemaker
  • History of cardiac pacemaker or implantable cardiac defibrillator
  • History of eating disorder
  • History of intrapyloric botulinum toxin injections
  • Subject is on chronic enteral or parenteral feeding
  • Subject has pronounced dehydration
  • Subject has evidence of severe cardiovascular autonomic neuropathy (e.g. history of recurrent syncope in the last 6 months)
  • Use of medications potentially influencing upper gastrointestinal motility or appetite within one week of the study (e.g., prokinetic drugs, macrolide antibiotics (erythromycin), GLP-1 mimetics)
  • Regular opiate use
  • Subjects who are taking drugs that potentially interact with olanzapine including diazepam, lorazepam, alcohol, carbamazepine, fluvoxamine, olanzapine and fluoxetine in combination, CNS acting drugs, levodopa and dopamine agonist, and olanzapine when used in combination with lithium or valproate
  • History or presence of clinically significant gastro-intestinal, hepatic or renal disease or other condition that would in the opinion of the investigator or medical monitor make the subject unsuitable for inclusion in this clinical study
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator would make the subject unsuitable for inclusion in this clinical study
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day time-period
  • Pregnant females as determined by positive serum or urine hCG test (from the first urine of the day) at screening or prior to dosing
  • Lactating females
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • Subject is unable to swallow pills
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01625923

Contacts
Contact: Allen Lee, MD (802) 847-4610
Contact: Braden Kuo, MD

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Braden Kuo, MD    617-726-0196      
Principal Investigator: Braden Kuo, MD         
United States, Vermont
University of Vermont Recruiting
Burlington, Vermont, United States, 05401
Contact: Allen Lee, MD    802-847-4610      
Principal Investigator: Allen Lee, MD         
Sponsors and Collaborators
University of Vermont
Massachusetts General Hospital
Investigators
Principal Investigator: Allen Lee, MD University of Vermont
Principal Investigator: Braden Kuo, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Allen Lee, Assistant Professor of Medicine, University of Vermont
ClinicalTrials.gov Identifier: NCT01625923     History of Changes
Other Study ID Numbers: ACG-SP-002-2012
Study First Received: June 18, 2012
Last Updated: April 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Vermont:
Gastroparesis
Idiopathic
Olanzapine

Additional relevant MeSH terms:
Gastroparesis
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Paralysis
Neurologic Manifestations
Signs and Symptoms
Olanzapine
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 22, 2014