Chronic Pancreatitis
Conditions
Keywords
Chronic Pancreatitis
Brief summary
* To determine if intravenous secretin administration in escalating doses three times daily for three days will improve the pain from CP at the time of infusion, after each infusion (1 to 3 hours), at Day 7 after infusion, and at Day 30 after infusion. * To validate the safety of intravenous secretin administration at the dosage indicated in this study.
Detailed description
12 patients will be enrolled in this study. Patients will be only those treated at Dartmouth-Hitchcock Medical Center for the diagnosis of CP. The diagnosis of CP will be made by the PI based on standard clinical, radiographic and/or biochemical criteria. Patients must be taking prescribed opioid analgesics for the specific treatment of CP at the time of study enrollment. Only patients between the ages of 18-70 and capable of providing informed consent will be considered eligible for the study.
Interventions
DRUGHuman Secretin
Dose Escalation
Sponsors
Dartmouth-Hitchcock Medical Center
ChiRhoClin, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, between the ages of 18-70 years old. 2. Documented chronic pancreatitis as determined by CT scan, endoscopic ultrasound, MRCP and/or pancreatic function tests. 3. If female, and not more than 1 year post-menopausal or surgically sterile, must use medically acceptable form of contraception or abstain from sexual activity during the study. Acceptable methods of birth control are: intrauterine device, implantable progesterone device, progesterone intramuscular injection, oral contraceptive (started at least one month prior to Screening Visit 1 and continuing for the duration of the trial), contraceptive patch, condoms with spermicide or abstinence. 4. If a female of reproductive potential, receive counseling on pregnancy protection and effective contraception within 30 days prior to dosing with secretin. 5. Negative serum pregnancy within 72 hours of secretin administration. 6. Use of opioid analgesics for chronic pain from CP. 7. Willing and able to sign written informed consent.
Exclusion criteria
1. Male or female \<18 or \>70 years of age. 2. Abnormal serum amylase and/or lipase indicative of acute pancreatitis within 30 days of study enrollment. 3. Exhibiting signs and/or symptoms of an episode of acute pancreatitis. 4. Severe cardiac disease (stable or unstable angina, congestive heart failure, uncontrolled arrhythmias, implantable defibrillator, severe valvular disease, etc). 5. Severe pulmonary disease (COPD, severe asthma, interstitial lung disease, etc). 6. Severe renal disease (history of acute or chronic renal failure, dialysis dependent, baseline creatinine \>2.0 mg/dL). 7. Previous adverse drug event to intravenous secretin. 8. Ongoing illicit drug use or abuse. 9. Ongoing moderate or severe alcohol use defined as greater than 8 oz beer, 8 oz wine and/or 1 oz liquor /day. 10. Acute pancreatitis as defined by the Atlanta Classification definition (refer to Table 1) within the previous two months or symptoms consistent with ongoing acute pancreatitis. 11. Prior pancreatic surgery. 12. Pregnant women, nursing mothers, or women of childbearing potential not employing appropriate contraception. 13. Use of medication that can potentially cause pancreatitis, such as metronidazole, tetracycline, sulfonamides within 30 days prior to Visit 1. 14. Any medical condition which, in the judgment of the investigator, renders participation in this study medically inadvisable. 15. Participation in an investigational clinical study for a drug or medical device within 30 days prior to Visit 1. 16. Unwilling or unable to give written, informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life at Baseline, Day 4 and Day 30. | Baseline, Day 4, Day 30. | Sf-36 ranges from 0 to 151. Higher scores indicating worse outcomes. |
| VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Baseline, Days 1, 2, 3, 4, 7, 30. | 10 point visual analog scale. 0= no pain. 10= worst possible pain. Days 1, 2, 3 were infusion days that included 5 VAS scores each day. |
| Opiate Use at Baseline, Days 4 and 30. | Baseline, Day 4, Day 30. | Daily opiate use (oral morphine equivalent). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events. | 30 Days | — |
| VAS Score at Each Administered Dose. | Days 1, 2, and 3. | 10 point scare from 0-10 with higher scores meaning higher levels of pain. VAS score assessed after each dose was summarized over Days 1, 2, and 3. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Human Secretin Human Secretin : Dose Escalation | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Uncooperative/unreliable | 1 |
Baseline characteristics
| Characteristic | Human Secretin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 42 years STANDARD_DEVIATION 9.7 |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 12 |
| serious Total, serious adverse events | 3 / 12 |
Outcome results
Primary
Opiate Use at Baseline, Days 4 and 30.
Daily opiate use (oral morphine equivalent).
Time frame: Baseline, Day 4, Day 30.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Human Secretin | Opiate Use at Baseline, Days 4 and 30. | Baseline | 139.6 mg/day | Standard Deviation 90.5 |
| Human Secretin | Opiate Use at Baseline, Days 4 and 30. | Day 4 | 127.0 mg/day | Standard Deviation 99.2 |
| Human Secretin | Opiate Use at Baseline, Days 4 and 30. | Day 30 | 97.2 mg/day | Standard Deviation 80.5 |
Comparison: Change from baseline to Day 4.p-value: 0.52t-test, 2 sided
Comparison: Change from baseline to Day 30.p-value: 0.34t-test, 2 sided
Primary
Quality of Life at Baseline, Day 4 and Day 30.
Sf-36 ranges from 0 to 151. Higher scores indicating worse outcomes.
Time frame: Baseline, Day 4, Day 30.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Human Secretin | Quality of Life at Baseline, Day 4 and Day 30. | Baseline | 100.92 units on a scale | Standard Deviation 5.26 |
| Human Secretin | Quality of Life at Baseline, Day 4 and Day 30. | Day 4 | 100.9 units on a scale | Standard Deviation 6.42 |
| Human Secretin | Quality of Life at Baseline, Day 4 and Day 30. | Day 30 | 101.45 units on a scale | Standard Deviation 5.68 |
Primary
VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30.
10 point visual analog scale. 0= no pain. 10= worst possible pain. Days 1, 2, 3 were infusion days that included 5 VAS scores each day.
Time frame: Baseline, Days 1, 2, 3, 4, 7, 30.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Baseline | 5.71 units on a scale | Standard Deviation 1.45 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 7 | 5.18 units on a scale | Standard Deviation 2.62 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 30 | 4.91 units on a scale | Standard Deviation 2.2 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 1 Pre-dose | 6.04 units on a scale | Standard Deviation 2.13 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 1 Dose 1 (.05mcg/kg) 100min post dose | 4.92 units on a scale | Standard Deviation 2.2 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 1 Dose 2 (.1mcg/kg) 100 min post dose | 4.87 units on a scale | Standard Deviation 2.06 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 1 Dose 3 (.2mcg/kg) 100 min post dose | 5.30 units on a scale | Standard Deviation 2.19 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 1 Dose 3 (.2mcg/kg) 380 min post dose | 4.64 units on a scale | Standard Deviation 2.68 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 2 Pre-dose | 5.33 units on a scale | Standard Deviation 2.3 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 2 Dose 1 (.1mcg/kg) 100min post dose | 5.25 units on a scale | Standard Deviation 1.88 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 2 Dose 2 (.2mcg/kg) 100min post dose | 5.50 units on a scale | Standard Deviation 1.71 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 2 Dose 3 (.4mcg/kg) 100min post dose | 4.67 units on a scale | Standard Deviation 2.32 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 2 Dose 3 (.4mcg/kg) 380min post dose | 4.77 units on a scale | Standard Deviation 2.6 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 3 Pre-dose | 4.92 units on a scale | Standard Deviation 2.36 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 3 Dose 1 (.2mcg/kg) 100min post dose | 4.58 units on a scale | Standard Deviation 2.15 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 3 Dose 2 (.4mcg/kg) 100min post dose | 4.33 units on a scale | Standard Deviation 2.11 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 3 Dose 3 (.8mcg/kg) 100min post dose | 5.17 units on a scale | Standard Deviation 2.44 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 3 Dose 3 (.8mcg/kg) 380min post dose | 4.71 units on a scale | Standard Deviation 2.47 |
| Human Secretin | VAS Score at Baseline, Days 1, 2, 3, 4, 7, 30. | Day 4 | 4.80 units on a scale | Standard Deviation 2.49 |
Comparison: Change from baseline to day 4.p-value: 0.25t-test, 2 sided
Comparison: Change from baseline to day 7.p-value: 0.19t-test, 2 sided
Comparison: Change from baseline to Day 30.p-value: 0.27t-test, 2 sided
Secondary
Number of Participants With Serious Adverse Events.
Time frame: 30 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Human Secretin | Number of Participants With Serious Adverse Events. | 3 participants |
Secondary
VAS Score at Each Administered Dose.
10 point scare from 0-10 with higher scores meaning higher levels of pain. VAS score assessed after each dose was summarized over Days 1, 2, and 3.
Time frame: Days 1, 2, and 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Human Secretin | VAS Score at Each Administered Dose. | .1 mcg/kg | 5.06 units on a scale | Standard Deviation 1.94 |
| Human Secretin | VAS Score at Each Administered Dose. | .2 mcg/kg | 4.92 units on a scale | Standard Deviation 2.14 |
| Human Secretin | VAS Score at Each Administered Dose. | .4 mcg/kg | 4.5 units on a scale | Standard Deviation 2.18 |
| Human Secretin | VAS Score at Each Administered Dose. | Pre-dose | 6.04 units on a scale | Standard Deviation 2.13 |
| Human Secretin | VAS Score at Each Administered Dose. | .05 mcg/kg | 4.92 units on a scale | Standard Deviation 2.2 |
| Human Secretin | VAS Score at Each Administered Dose. | .8 mcg/kg | 5.36 units on a scale | Standard Deviation 2.46 |