A Pilot Study on the Efficacy and Safety of Olanzapine in Gastroparesis
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.
|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|
- 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.
- 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.
|Study Start Date:||January 2013|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
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.
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01625923
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, Michigan|
|University of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Allen Lee, MD||University of Michigan|
|Principal Investigator:||Braden Kuo, MD||Massachusetts General Hospital|
|Principal Investigator:||William Hasler, MD||University of Michigan|