The purpose of this study is to determine if study drug (Pioglitazone) treatment will improve pre-diabetes (insulin resistance) or ealy diabetes and improve clinical symptoms (pain) or laboratory evidence of chronic pancreatitis. The goal of the investigators is to gather information from this study to help gain understanding of a potential therapy for chronic pancreatitis.
The pancreas is a digestive organ that secretes insulin (and other hormones) into the blood for regulating blood sugar (glucose) and digestive enzymes into the intestine for digesting and absorbing nutrients consumed in meals. Chronic pancreatitis is a progressive clinical disease of the pancreas, associated with swelling (inflammation), scarring (fibrosis) and loss of normal functioning tissue. Patients develop diabetes mellitus (elevated blood sugar), malabsorption of nutrients, weight loss and pain. Presently chronic pancreatitis is considered an irreversible condition because the mechanisms responsible for chronic pancreatitis are poorly understood and no therapy is proven. However, recent studies provide important clues that oral medications (Thiazolidinediones) used to treat diabetes mellitus might improve or reverse features of chronic pancreatitis, including elevated sugar or diabetes, reduced secretion of digestive enzymes, and pancreatic swelling and scarring. Note: Takeda Pharmaceuticals North America (TPNA) provided pioglitazone and placebo pills with identically appearance until June 28, 2010, approximately the middle of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
64
Participants randomized to pioglitazone receive 30 mg taken once daily for 48 weeks.
University of Michigan Health System
Ann Arbor, Michigan, United States
Glucose Tolerance at 24 Weeks
1. Normal = normal plasma glucose and normal glucose tolerance (OGTT). 2. Impaired category includes all non-diabetic participants with either a) Impaired fasting glucose = fasting plasma glucose \>110 mg/dl and \<126 mg/dl; or b) Impaired glucose intolerance = 2-hour plasma glucose (OGTT) \>140 mg/dl and \<200 mg/dl. 3. Diabetes = fasting plasma glucose \>126 mg/dl 2-hour (OGTT) plasma glucose \>200 mg/dl.
Time frame: 24 weeks
Glucose Tolerance at 48 Weeks
1. Normal = normal plasma glucose and normal glucose tolerance (OGTT). 2. Impaired category includes all non-diabetic participants with either a) Impaired fasting glucose = fasting plasma glucose \>110 mg/dl and \<126 mg/dl; or b) Impaired glucose intolerance = 2-hour plasma glucose (OGTT) \>140 mg/dl and \<200 mg/dl. 3. Diabetes = fasting plasma glucose \>126 mg/dl 2-hour (OGTT) plasma glucose \>200 mg/dl.
Time frame: 48 weeks
Insulin Sensitivity Index for Glycemia at 24 Weeks
Insulin Sensitivity = Index for Glycemia (ISI gly) = 2 / (\[INSp x GLYp\] + 1). GLYp = Glycemic 0-2 hr area = sum of normalized (based on institutional values) 0 \& 2 hr glucose. INSp = Insulinemic 0-2 hr area = sum of normalized (based on institutional values) 0 \& 2 hr insulin.
Time frame: 24 weeks
Insulin Sensitivity Index for Glycemia at 48 Weeks.
Insulin Sensitivity = Index for Glycemia (ISI gly) = 2 / (\[INSp x GLYp\] + 1). GLYp = Glycemic 0-2 hr area = sum of normalized (based on institutional values) 0 \& 2 hr glucose. INSp = Insulinemic 0-2 hr area = sum of normalized (based on institutional values) 0 \& 2 hr insulin.
Time frame: 48 weeks
Beta-cell Function
Homeostasis model assessment (HOMA 2) values generated using calculator at https://www.dtu.ox.ac.uk/homacalculator/
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 24, 48 weeks
Insulin Resistance at 24 and 48 Weeks
Homeostasis model assessment (HOMA 2) values generated using calculator at https://www.dtu.ox.ac.uk/homacalculator/
Time frame: 24, 48 weeks
Pancreas Ultrasound Appearance
Mean score on a scale of 0 - 10: count of positive Endoscopic Ultrasound(EUS) features: Parenchymal Features - Only Body and Tail 1. Calcification (\>3 hyperechoic foci \>2 mm length \& width with shadowing) 2. Lobularity (\>3 well-circumscribed, \>5mm structures) 3. Hyperechoic stranding (\>3 hyperechoic lines \>3mm in length, seen in \> 2 different directions with respect to the imaged plane Parenchymal Features - Head, Body and Tail 4. Cyst (\>2 mm diameter anechoic round or oval structure) 5. Hyperechoic foci (\>3 reflectors, \>3 mm long \& wide, no shadowing) Ductal Features - Only Body and Tail 6. Side Branch Dilation (\>3 tubular, anechoic, \>1 mm structures,Main pancreatic duct (MPD) connects) 7. Irregular MPD contour (uneven and ectatic in its course) 8. Hyperechoic MPD margin (hyperechoic in \>50% of MPD) 9. Dilation MPD (\>3.5 mm body, \>1.5 mm tail\*) Ductal Features - Head, Body and Tail 10. MPD calculi (hyperechoic foci with shadowing contained within MPD)
Time frame: 48 weeks
Quality of Life
The SF36 (Short Form with 36 questions) QoL scoring system has 36 questions, comprising two main dimensions (Physical Health and Mental Health), further divided by 8 independent scales (Physical functioning, Role-Physical, Bodily pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health). The scales for general health and mental health overlap components of both the two main dimensions (Physical Health and Mental Health). The scales, including the total score and dimensions are scored as a number between 0 and 100, where 0 represents lower limits of functioning and 100 is best functioning possible. Data reported is the average total score.
Time frame: 24, 48 weeks
Number and Percentage of Participants With Steatorrhea
Participants were counted as having steatorrhea if they had either a) positive qualitative fecal fat; or b) 72 hour quantitative fecal fat result with \>7g fat in stool in 24hours
Time frame: 48 weeks
Pain
Pain is reported as the mean of four Visual analogue scales, ranging from 0 points (no pain) to 100 points (severe pain) 1. What is your pain right now? 2. What is your typical or average pain in the last 12 weeks? 3. What is your pain level at its best in the last 12 weeks (how close to "0" does your pain get at its best)? 4. What is your pain level at its worst in the last 12 weeks (how close to "0" does your pain get at its worst)?
Time frame: 12, 24, 36, 48 and 60 weeks
Body Mass Index (BMI)
standard BMI defined as mass in kilograms divided by height in meters squared
Time frame: 12, 24, 36, 48 and 60 weeks
Hospitalizations
Mean number of hospitalizations within the prior 12 weeks
Time frame: 12, 24, 36, 48 and 60 weeks
Missed Work
Mean days of missed work reported by participants in response to question asking about missed work since the last visit (12 weeks)
Time frame: 12, 24, 36, 48, 60 weeks
Insulin Sensitivity (%S)
Homeostasis model assessment (HOMA 2) values generated using calculator at https://www.dtu.ox.ac.uk/homacalculator/;
Time frame: 24 and 48 weeks