Pioglitazone for Idiopathic Gastroparesis

Early Phase 1

Completed

Conditions: Gastroparesis

Interventions: Drug: Pioglitazone 30 mg

Registration Number: NCT04300127

Lead Sponsor: Johns Hopkins University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pioglitazone	Pioglitazone 30 mg	Candidates who after the screening period are eligible to receive Pioglitazone

Primary Outcome Measures

Name	Time	Method
Severity of Gastrointestinal Symptoms as Assessed by the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index	Baseline, later monthly up to 3 months.	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 (GCSI) 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. Values reported represent the mean participant scale choice.

Secondary Outcome Measures

Name	Time	Method
Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM)	Baseline and later monthly up to 3 months	The Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) questionnaire is a patient-reported tool designed to evaluate the severity of upper gastrointestinal symptoms across multiple domains, including nausea/vomiting, postprandial fullness/early satiety, bloating, upper abdominal pain, and heartburn/regurgitation. Each symptom is rated on a 0 to 5 Likert scale, where 0 indicates no symptoms and 5 represents very severe symptoms, with higher scores reflecting worse symptom severity. The total PAGI-SYM score is typically calculated as the average of individual domain scores, resulting in a possible score range of 0 to 5. The mean participant scale choice is reported.
Functional Status as Assessed by the SF-36v2 Health Survey	Baseline, later monthly up to 3 months	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.
C- Reactive Protein Level in Blood	Baseline and 2 months after treatment initiation.	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.
Erythrocyte Sedimentation Rate (ESR)	Baseline and 2 months after treatment initiation	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. Values above these ranges are considered worse.
Mood as Assessed by the Beck Depression Inventory	Baseline, later monthly up to 3 months	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 range is 0-63. Higher total scores indicate more severe depressive symptoms.
Mood as Assessed by the State-Trait Anxiety Inventory	Baseline, later monthly up to 3 months	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.