Clinical trial NCT04300127: Pioglitazone for Idiopathic Gastroparesis
Official title: Pioglitazone for the Treatment of Idiopathic Gastroparesis (PIOGAS Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Gastroparesis
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2020-03-09
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Pilot study
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Severity of Gastrointestinal Symptoms as Assessed by the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index
timeFrame: Baseline, later monthly up to 3 months.
Secondary outcomes:
measure: Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM)
timeFrame: Baseline and later monthly up to 3 months
measure: Functional Status as Assessed by the SF-36v2 Health Survey
timeFrame: Baseline, later monthly up to 3 months
measure: C- Reactive Protein Level in Blood
timeFrame: Baseline and 2 months after treatment initiation.
measure: Erythrocyte Sedimentation Rate (ESR)
timeFrame: Baseline and 2 months after treatment initiation
measure: Mood as Assessed by the Beck Depression Inventory
timeFrame: Baseline, later monthly up to 3 months
measure: Mood as Assessed by the State-Trait Anxiety Inventory
timeFrame: Baseline, later monthly up to 3 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Glenn J Treisman, MD
role: PRINCIPAL_INVESTIGATOR
References: