Trial Outcomes & Findings for Chronic Pancreatitis. Effect of Pioglitazone on Endocrine Function, Exocrine Function & Structure, Pain & Life Quality (NCT NCT00782795)

NCT ID: NCT00782795

Last Updated: 2018-01-11

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 64 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2018-01-11

Participant Flow

39 screen fails did not go on to randomization

Participant milestones

Measure	Pioglitazone 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Sugar Pill (Placebo) 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Overall Study STARTED	17	8
Overall Study 6 Weeks (1st Apptment)	16	7
Overall Study 24 Week Appointment	16	7
Overall Study COMPLETED	16	6
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Pioglitazone 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Sugar Pill (Placebo) 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Overall Study Withdrawal by Subject	1	2

Baseline Characteristics

Chronic Pancreatitis. Effect of Pioglitazone on Endocrine Function, Exocrine Function & Structure, Pain & Life Quality

Baseline characteristics by cohort

Measure	Pioglitazone n=17 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Sugar Pill (Placebo) n=8 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Total n=25 Participants Total of all reporting groups
Age, Continuous	52.35 years STANDARD_DEVIATION 7.61 • n=5 Participants	48.37 years STANDARD_DEVIATION 9.83 • n=7 Participants	51.08 years STANDARD_DEVIATION 8.39 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	6 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment United States	17 participants n=5 Participants	8 participants n=7 Participants	25 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Sugar Pill (Placebo) n=7 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Glucose Tolerance at 24 Weeks Diabetes	2 Participants	4 Participants
Glucose Tolerance at 24 Weeks Impaired Glucose Tolerance	3 Participants	4 Participants
Glucose Tolerance at 24 Weeks Normal	2 Participants	8 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Sugar Pill (Placebo) n=6 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Glucose Tolerance at 48 Weeks Diabetes	2 Participants	5 Participants
Glucose Tolerance at 48 Weeks Impaired Glucose Tolerance	2 Participants	5 Participants
Glucose Tolerance at 48 Weeks Normal	2 Participants	6 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Sugar Pill (Placebo) n=7 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Insulin Sensitivity Index for Glycemia at 24 Weeks	0.26 numeric index Standard Deviation 0.11	0.35 numeric index Standard Deviation 0.20

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Sugar Pill (Placebo) n=6 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Insulin Sensitivity Index for Glycemia at 48 Weeks.	0.21 numeric index Standard Deviation 0.13	0.36 numeric index Standard Deviation 0.18

SECONDARY outcome

Timeframe: 24, 48 weeks

Population: 1 participant on the placebo side was no longer participating at 48 weeks

Homeostasis model assessment (HOMA 2) values generated using calculator at https://www.dtu.ox.ac.uk/homacalculator/

Outcome measures

Measure	Sugar Pill (Placebo) n=7 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Beta-cell Function week 24	110.51 Beta-cell function (%) Standard Deviation 31.59	120.59 Beta-cell function (%) Standard Deviation 48.78
Beta-cell Function week 48	121.60 Beta-cell function (%) Standard Deviation 61.53	120.68 Beta-cell function (%) Standard Deviation 44.39

SECONDARY outcome

Timeframe: 24, 48 weeks

Population: 1 participant on the placebo side was no longer participating at 48 weeks

Homeostasis model assessment (HOMA 2) values generated using calculator at https://www.dtu.ox.ac.uk/homacalculator/

Outcome measures

Measure	Sugar Pill (Placebo) n=7 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Insulin Resistance at 24 and 48 Weeks 24 weeks	2.56 HOMA2-IR Standard Deviation 1.29	2.27 HOMA2-IR Standard Deviation 1.00
Insulin Resistance at 24 and 48 Weeks 48 weeks	2.32 HOMA2-IR Standard Deviation 0.85	2.42 HOMA2-IR Standard Deviation 1.31

SECONDARY outcome

Timeframe: 48 weeks

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)

Outcome measures

Measure	Sugar Pill (Placebo) n=6 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Pancreas Ultrasound Appearance	4.5 units on a scale Interval 4.0 to 5.0	4.91 units on a scale Interval 3.5 to 6.0

SECONDARY outcome

Timeframe: 24, 48 weeks

Population: The 24 week data has two participants' data missing from each arm because it was not available.

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.

Outcome measures

Measure	Sugar Pill (Placebo) n=6 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Quality of Life week 24	67.74 units on a scale Standard Deviation 29.13	70.06 units on a scale Standard Deviation 18.86
Quality of Life week 48	66.0 units on a scale Standard Deviation 26.33	64.71 units on a scale Standard Deviation 23.54

SECONDARY outcome

Timeframe: 48 weeks

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

Outcome measures

Measure	Sugar Pill (Placebo) n=6 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Number and Percentage of Participants With Steatorrhea	1 Participants	5 Participants

SECONDARY outcome

Timeframe: 12, 24, 36, 48 and 60 weeks

Population: Some participant data is missing from some weeks, due to incomplete forms in certain instances.

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)?

Outcome measures

Measure	Sugar Pill (Placebo) n=7 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Pain week 12	19.38 units on a scale Standard Deviation 21.46	23.03 units on a scale Standard Deviation 25.16
Pain week 24	26.32 units on a scale Standard Deviation 28.84	18.92 units on a scale Standard Deviation 22.71
Pain week 36	22.88 units on a scale Standard Deviation 21.97	23.55 units on a scale Standard Deviation 23.29
Pain week 48	25.42 units on a scale Standard Deviation 26.52	27.50 units on a scale Standard Deviation 27.88
Pain week 60	13.15 units on a scale Standard Deviation 16.08	26.11 units on a scale Standard Deviation 24.61

SECONDARY outcome

Timeframe: 12, 24, 36, 48 and 60 weeks

Population: Some participant data is missing from some weeks, due to incomplete forms in certain instances.

standard BMI defined as mass in kilograms divided by height in meters squared

Outcome measures

Measure	Sugar Pill (Placebo) n=6 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Body Mass Index (BMI) 12 weeks	28.02 kg/m^2 Standard Deviation 5.73	28.64 kg/m^2 Standard Deviation 6.88
Body Mass Index (BMI) 24 weeks	25.56 kg/m^2 Standard Deviation 4.46	29.49 kg/m^2 Standard Deviation 6.36
Body Mass Index (BMI) 36 weeks	28.55 kg/m^2 Standard Deviation 5.92	27.46 kg/m^2 Standard Deviation 6.01
Body Mass Index (BMI) 48 weeks	28.26 kg/m^2 Standard Deviation 6.36	28.75 kg/m^2 Standard Deviation 6.92
Body Mass Index (BMI) 60 weeks	29.20 kg/m^2 Standard Deviation 4.36	27.94 kg/m^2 Standard Deviation 6.77

SECONDARY outcome

Timeframe: 12, 24, 36, 48 and 60 weeks

Population: Some participant data is missing from some weeks, due to incomplete forms in certain instances.

Mean number of hospitalizations within the prior 12 weeks

Outcome measures

Measure	Sugar Pill (Placebo) n=7 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Hospitalizations week 12	0 hospitalizations Standard Deviation 0	0.06 hospitalizations Standard Deviation 0.25
Hospitalizations week 24	0.43 hospitalizations Standard Deviation 1.13	0.06 hospitalizations Standard Deviation 0.25
Hospitalizations week 36	0.20 hospitalizations Standard Deviation 0.45	0.07 hospitalizations Standard Deviation 0.26
Hospitalizations week 48	0 hospitalizations Standard Deviation 0	0.12 hospitalizations Standard Deviation 0.34
Hospitalizations week 60	0 hospitalizations Standard Deviation 0	0.06 hospitalizations Standard Deviation 0.25

SECONDARY outcome

Timeframe: 12, 24, 36, 48, 60 weeks

Population: Some participant data is missing from some weeks, due to incomplete forms in certain instances.

Mean days of missed work reported by participants in response to question asking about missed work since the last visit (12 weeks)

Outcome measures

Measure	Sugar Pill (Placebo) n=7 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Missed Work week 12	0.50 days Standard Deviation 1.20	0 days Standard Deviation 0
Missed Work week 24	0.71 days Standard Deviation 1.89	0.75 days Standard Deviation 2.52
Missed Work week 36	0.20 days Standard Deviation 0.45	0.47 days Standard Deviation 1.36
Missed Work week 48	0 days Standard Deviation 0	0.5 days Standard Deviation 1.75
Missed Work week 60	0 days Standard Deviation 0	0.25 days Standard Deviation 1

SECONDARY outcome

Timeframe: 24 and 48 weeks

Population: 1 participant on the placebo side was no longer participating at 48 weeks

Homeostasis model assessment (HOMA 2) values generated using calculator at https://www.dtu.ox.ac.uk/homacalculator/;

Outcome measures

Measure	Sugar Pill (Placebo) n=7 Participants 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Pioglitazone n=16 Participants 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Insulin Sensitivity (%S) 24 weeks	45.39 insulin sensitivity (%) Standard Deviation 17.26	51.83 insulin sensitivity (%) Standard Deviation 20.42
Insulin Sensitivity (%S) 48 weeks	48.12 insulin sensitivity (%) Standard Deviation 17.21	46.18 insulin sensitivity (%) Standard Deviation 26.86

Adverse Events

Pioglitazone

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Sugar Pill (Placebo)

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pioglitazone n=17 participants at risk 30 mg pioglitazone (Actos) tablet taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.	Sugar Pill (Placebo) n=8 participants at risk 1 sugar pill (placebo) taken once daily for 48 weeks. Pioglitazone: Participants will be randomized to either pioglitazone or placebo. The dosing is 30 mg taken once daily for 48 weeks.
Ear and labyrinth disorders chronic vertigo exacerbation	5.9% 1/17 • 48 weeks All adverse events that participants raised to study team as such, all of which were reported on to the IRB, are shown below.	0.00% 0/8 • 48 weeks All adverse events that participants raised to study team as such, all of which were reported on to the IRB, are shown below.
Gastrointestinal disorders Abdominal Pain	17.6% 3/17 • Number of events 8 • 48 weeks All adverse events that participants raised to study team as such, all of which were reported on to the IRB, are shown below.	12.5% 1/8 • Number of events 3 • 48 weeks All adverse events that participants raised to study team as such, all of which were reported on to the IRB, are shown below.
Endocrine disorders Hyperglycemia	0.00% 0/17 • 48 weeks All adverse events that participants raised to study team as such, all of which were reported on to the IRB, are shown below.	12.5% 1/8 • 48 weeks All adverse events that participants raised to study team as such, all of which were reported on to the IRB, are shown below.
Nervous system disorders Trauma to head	5.9% 1/17 • 48 weeks All adverse events that participants raised to study team as such, all of which were reported on to the IRB, are shown below.	0.00% 0/8 • 48 weeks All adverse events that participants raised to study team as such, all of which were reported on to the IRB, are shown below.
Respiratory, thoracic and mediastinal disorders Pneumonia	5.9% 1/17 • 48 weeks All adverse events that participants raised to study team as such, all of which were reported on to the IRB, are shown below.	0.00% 0/8 • 48 weeks All adverse events that participants raised to study team as such, all of which were reported on to the IRB, are shown below.
Skin and subcutaneous tissue disorders non-specific neck swelling	5.9% 1/17 • 48 weeks All adverse events that participants raised to study team as such, all of which were reported on to the IRB, are shown below.	0.00% 0/8 • 48 weeks All adverse events that participants raised to study team as such, all of which were reported on to the IRB, are shown below.

Other adverse events

Adverse event data not reported

Additional Information

Matthew DiMagno

University of Michigan

Email: mdimagno@umich.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place