Pioglitazone for Idiopathic Gastroparesis

Study Overview
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Brief Summary
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The principal objective of this pilot study will be to evaluate whether 8 weeks of treatment of pioglitazone will improve symptoms as measured by the Gastrointestinal Symptom Index (GCSI) in patients with Idiopathic Gastroparesis.

Detailed Description
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Objective • The principal objective of this pilot study will be to evaluate whether 8 weeks of treatment of pioglitazone will improve symptoms as measured by the Gastrointestinal Symptom Index Daily Diary (GCSI-DD) in patients with Idiopathic Gastroparesis Secondary objectives of this study include: To determine the effects of pioglitazone on other symptoms associated with gastroparesis using the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) and the Gastrointestinal Symptom Rating Scale (GSRS), To determine the effects of pioglitazone on gastric emptying as measured by the 13C- Spirulina breath test, To determine the effects of pioglitazone on satiety as measured by a liquid caloric test To determine the effects of pioglitazone on depression and anxiety using the Beck Depression Inventory and State-Trait Anxiety Scores, To determine the effects of pioglitazone on Quality of Life using the PAGI-QoL and Short Form (SF)-36 questionnaire, To determine the effects of pioglitazone on markers of inflammation (CRP and ESR) and serum cytokine levels To determine the nature and incidence of adverse effects from a 12-week course of pioglitazone. Treatment group • Pioglitazone (30 mg po qd) Population • Age 18 years or older at registration with nausea, vomiting, and other symptoms suggestive of patients with chronic nausea and vomiting of presumed gastric origin, with symptomatic gastroparesis. Study duration Up to 4 weeks of screening prior to pioglitazone treatment 8 weeks of treatment starting at initial dose of pioglitazone 4 weeks of washout period Length of recruitment: 16 months Sample size justification Total of 10 patients Primary comparison: Baseline PAGI-SYM score versus 4, 8, and 12 weeks. Number of clinical centers • Johns Hopkins Bayview Medical Center.

Official Title
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Pioglitazone for the Treatment of Idiopathic Gastroparesis (PIOGAS Study)

Conditions
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Gastroparesis

Intervention / Treatment
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* Drug: Pioglitazone 30 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older at registration Diagnosis of gastroparesis as documented by gastric emptying scintigraphy (4-hour emptying after a low-fat meal with any combination of 2 and 4 hour retention of >60% and 10% respectively) Ongoing symptoms referable to gastroparesis (i.e. Nausea and vomiting, bloating, and abdominal pain) Exclusion of other causes of symptoms such as mechanical gastrointestinal obstruction, uncontrolled esophagitis, peptic ulcer disease, etc. By standard radiographic or endoscopic tests Females will be required to use adequate contraceptive methods during study participation as determined by the Principal Investigator and the study team members Exclusion Criteria: Another active disorder, which could explain symptoms in the opinion of the investigator Age < than 18 years Pregnancy or nursing Previous surgery of the upper gastrointestinal tract, including vagotomy Another active disorder, which could explain symptoms in the opinion of the investigator Use of narcotics more than 3 days per week Significant hepatic injury as defined by significant alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations of greater than 2 x upper limit of normal (ULN) or a Child-Pugh score of 10 or greater Serious systemic disease, such as recent myocardial infarction/unstable angina, decompensated congestive heart failure, severe pulmonary disease with dyspnea at rest, or altered mental status from any cause Diabetes as defined by HbA1c >6.5 and/or fasting blood sugar of >125 mg/DL Contraindications to pioglitazone such as hypersensitivity or allergy Concurrent use of: estradiol, ethynyl estradiol, mestranol, pazopanib, warfarin, digoxin, atorvastatin, ranitidine, gemfibrozil, fexofenadine, midazolam Any other condition, which in the opinion of the investigator would impede compliance or hinder the completion of the study History of bladder cancer or family history of bladder cancer Failure to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pioglitazone<br>Candidates who after the screening period are eligible to receive Pioglitazone | Drug: Pioglitazone 30 mg<br>* Patients will received 30 mg of Pioglitazone once a day for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Severity of gastrointestinal symptoms as assessed by the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary | The effect of Pioglitazone on nausea, early satiety, postprandial fullness, and upper abdominal pain as per changes in patient scoring in The American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary (ANMS GCSI-DD) which has been designed to assess symptoms associated with gastroparesis. Symptoms are rated as none (0), mild (1), moderate (2), severe (3), very severe (4) scale of the worst severity of the symptom over the last 24 hours. | Daily up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of Life as assessed by the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life scale | The effect of Pioglitazone on quality of life assessed by the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QoL). The PAGI-QOL instrument consists of 30 items, each with response options based on a 6-point scale and with a recall period of the previous 2 weeks. The items are grouped into 5 dimensions: Daily Activities, Clothing, Diet and Food Habits, Relationship and Psychological Well-being and Distress. A score per dimension as well as a total score can be calculated. The PAGI-QOL scores range from 0 (lowest QoL) to 5 (highest QoL). | 1 day before treatment and 12 weeks after treatment | 
| Change in Functional status as assessed by the SF-36v2 Health Survey | The effect of Pioglitazone on quality of life assessed by the SF-36v2 Health Survey. The SF-36v2 is a 36-item, self-report measure designed to assess quality of life in patients. This measure also provides two summary scores (physical and mental health) and eight scale scores. The eight sections are: vitality, physical functioning, bodily pain and general health perceptions, physical role functioning, emotional role functioning, social role functioning and mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability, i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | 1 day before treatment and 12 weeks after treatment | 
| Change in C- reactive protein level in blood | The effect of Pioglitazone on Inflammatory markers as per changes in the values of C reactive protein (CRP) in blood. Normal CRP levels are below 3.0 mg/L. | 1 day before treatment and after 8 weeks of treatment | 
| Change in Erythrocyte Sedimentation Rate | The effect of Pioglitazone on Inflammatory markers as per changes Erythrocyte Sedimentation Rate (ESR) in blood. Results are reported as the millimeters of clear fluid (plasma) that are present at the top portion of the tube after one hour. The normal range is 0 to 22 mm/hr for men and 0 to 29 mm/hr for women. | 1 day before treatment and after 8 weeks of treatment | 
| Change in Mood as assessed by the Beck Depression Inventory | The effect of Pioglitazone on mood as per changes in the score of Beck Depression Inventory (BDI-II). The BDI-II is a commonly used, reliable 21-item self-report measure designed to assess for depression. Individuals are asked to respond to each question based on a two-week time period. The BDI-II is widely used as an indicator of the severity of depression, but not as a diagnostic tool. BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on the severity of each item. The maximum total score is 63. | 1 day before treatment and 12 weeks after treatment | 
| Change in Mood as assessed by the State-Trait Anxiety Inventory | The effect of Pioglitazone on mood as per changes in the score of the State-Trait Anxiety Inventory (STAI). The STAI is a 40-item self-report measure designed to assess anxiety. This measure provides two subscale scores (State and Trait). STAI is one of the first tests to assess both state and trait anxiety separately. Each type of anxiety has its own scale of 20 different questions that are scored. Scores range from 20 to 80, with higher scores correlating with greater anxiety. | 1 day before treatment and 12 weeks after treatment | 
| Change in Behavior as assessed by the Beck Depression Inventory | The effect of Pioglitazone on behavior as per changes in the score of Beck Depression Inventory (BDI-II). The BDI-II is a commonly used, reliable 21-item self-report measure designed to assess for depression. Individuals are asked to respond to each question based on a two-week time period. The BDI-II is widely used as an indicator of the severity of depression, but not as a diagnostic tool. BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on the severity of each item. The maximum total score is 63. | 1 day before treatment and 12 weeks after treatment | 
| Change in Behavior as assessed by the State-Trait Anxiety Inventory | The effect of Pioglitazone on behavior as per changes in the score of the State-Trait Anxiety Inventory (STAI). The STAI is a 40-item self-report measure designed to assess anxiety. This measure provides two subscale scores (State and Trait). STAI is one of the first tests to assess both state and trait anxiety separately. Each type of anxiety has its own scale of 20 different questions that are scored. Scores range from 20 to 80, with higher scores correlating with greater anxiety. | 1 day before treatment and 12 weeks after treatment |