Pioglitazone for Idiopathic Gastroparesis

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 23 patients
• Primary comparison: Baseline PAGI-SYM score versus 4, 8, and 12 weeks.

Number of clinical centers

• Johns Hopkins Bayview Medical Center.

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