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

NCT01625923 | Terminated Results

• 1 other identifier: ACG-SP-002-2012
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Idiopathic Gastroparesis

Keywords

Gastroparesis; Idiopathic; Olanzapine

Outcome Measures

Primary Outcomes (3)

• Change in Mean BMI

  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.

  8 weeks

• Mean GCSI-DD Before/After Treatment With Olanzapine

  The investigators will utilize the gastroparesis cardinal symptom index daily diary (GCSI-DD) to compare severity of symptoms before and after treatment with olanzapine. The total GCSI-DD is a validated questionnaire that measures the daily relevant symptoms of gastroparesis and ranges from 0 (no symptoms) to 5 (severe symptoms).

  8 weeks

• Change in Mean Serum Glucose

  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.

  8 weeks

Secondary Outcomes (2)

• Change in Mean Gastric Emptying Time

  8 weeks

• Change in Mean Ghrelin Levels Over Time

  8 weeks

Study Arms (1)

Olanzapine

EXPERIMENTAL

An open-label pilot study of 20 consecutive subjects ages 18 - 70 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

Interventions

Olanzapine DRUG

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.

Also known as: Zyprexa

Olanzapine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between 18 and 70 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 - 30 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan: lead
• Massachusetts General Hospital: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Gastroparesis

Interventions

Olanzapine

Condition Hierarchy (Ancestors)

Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Allen Lee
• Organization: University of Michigan

allenlee@umich.edu

734-936-9454

Study Officials

• Allen Lee, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Braden Kuo, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• William Hasler, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Lecturer

Study Record Dates

• First Submitted: June 18, 2012
• First Posted: June 22, 2012
• Study Start: January 1, 2013
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: September 10, 2019
• Results First Posted: September 10, 2019

Record last verified: 2019-08

Locations

US (2)