Idiopathic GastroparesisNCT01625923
A Pilot Study on the Efficacy and Safety of Olanzapine in Gastroparesis
A study testing Olanzapine in people with Idiopathic Gastroparesis, run by University of Michigan at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Idiopathic Gastroparesis
- What is being tested?
- Olanzapine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2013to Jun 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Michigan
Ann Arbor, Michigan, 48109
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: A Pilot Study on the Efficacy and Safety of Olanzapine in Improving Symptoms and Gastric Motility 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.
- Conditions
- Idiopathic Gastroparesis
- Being tested
- Olanzapine
- Keywords
- Gastroparesis, Idiopathic, Olanzapine
- Medical subject headings
- Gastroparesis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlanzapineDrug
Also called Zyprexa
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Olanzapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
Measured: 8 weeks
Secondary outcomes (2)
Change in Mean Gastric Emptying Time
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.
Measured: 8 weeks
Change in Mean Ghrelin Levels Over Time
The investigators seek to determine whether olanzapine promotes secretion of ghrelin in gastroparesis.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2012 (estimated)
- Study startJan 2013
- Primary completionJun 2019
- Study completionJun 2019
Why it stopped: Inadequate recruitment numbers
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Idiopathic GastroparesisStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital
- Responsible party
- Principal investigator, Allen Lee, University of Michigan
- Investigators
- Allen Lee, MD, Principal investigator, University of MichiganBraden Kuo, MD, Principal investigator, Massachusetts General HospitalWilliam Hasler, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01625923
- Sponsor's protocol ID
- ACG-SP-002-2012
- Status last verified
- Aug 2019
- First submitted
- 18 Jun 2012
- Last updated
- 10 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study on the Efficacy and Safety of Olanzapine in Improving Symptoms and Gastric Motility in Gastroparesis
- ClinicalTrials.gov ID
- NCT01625923
- Acronym / sponsor ID
- ACG-SP-002-2012
- Conditions
- Idiopathic Gastroparesis
- Keywords
- Gastroparesis, Idiopathic, Olanzapine
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate recruitment numbers
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital
- Study start
- Jan 2013
- Primary completion
- Jun 2019 (actual)
- Study completion
- Jun 2019 (actual)
- First posted
- 22 Jun 2012 (estimated)
- Results
- Posted 10 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olanzapine | Experimental | Drug: OlanzapineAn 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlanzapineAlso: ZyprexaSubjects 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. | Drug | Olanzapine |
Primary outcome
Change in Mean BMI
Time frame: 8 weeks
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.
Mean GCSI-DD Before/After Treatment With Olanzapine
Time frame: 8 weeks
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).
Change in Mean Serum Glucose
Time frame: 8 weeks
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.
2 secondary outcomes
Change in Mean Gastric Emptying Time
Time frame: 8 weeks
Change in Mean Ghrelin Levels Over Time
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Idiopathic Gastroparesis
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingObservational study
Pyloric Sphincter Abnormalities in Patients With Gastroparesis Symptoms
Gastroparesis, Idiopathic Gastric Motility Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allen Lee, MD principal investigator
University of Michigan
Braden Kuo, MD principal investigator
Massachusetts General Hospital
William Hasler, MD principal investigator
University of Michigan
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Olanzapine in people with Idiopathic Gastroparesis, run by University of Michigan at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Mean BMI (time frame: 8 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2019.