Intraductal Liposomal Bupivacaine for Chronic Pancreatitis
Primary Purpose
Chronic Pancreatitis
Status
Withdrawn
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
ERCP with Bupivacaine infusion
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Pancreatitis
Eligibility Criteria
Inclusion Criteria:
- Signed Informed consent
- Age >18 years
- Patients with an established diagnosis of chronic pancreatitis with constant daily pain consistent with the same and not relieved despite standard clinical care for at least 6 months and in whom ERCP is indicated for standard of care.
Exclusion Criteria:
- Significant liver or renal dysfunction.
- Any Contraindication of ERCP.
Sites / Locations
- Johns Hopkins Hopital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Bupivacaine arm
Arm Description
Participants undergoing ERCP as part of routine clinical care will be consented for this study.
Outcomes
Primary Outcome Measures
Change in the pain score at 24 hours after ERCP
Raw pain score using a visual analog scale from 0 to 10, being 0 no pain and 10 the worst pain the participant can imagine.
Secondary Outcome Measures
Change in the pain score at 2 hours after ERCP
Raw pain score using a visual analog scale from 0 to 10, being 0 no pain and 10 the worst pain the participant can imagine.
Change in the pain score at 48 hours after ERCP
Raw pain score using a visual analog scale from 0 to 10, being 0 no pain and 10 the worst pain the participant can imagine.
Change in the pain score at 72 hours after ERCP
Raw pain score using a visual analog scale from 0 to 10, being 0 no pain and 10 the worst pain the participant can imagine.
Full Information
NCT ID
NCT04611958
First Posted
October 27, 2020
Last Updated
July 15, 2021
Sponsor
Johns Hopkins University
1. Study Identification
Unique Protocol Identification Number
NCT04611958
Brief Title
Intraductal Liposomal Bupivacaine for Chronic Pancreatitis
Official Title
Intraductal Liposomal Bupivacaine as a Therapeutic Trial to Determine the Contribution of Peripheral Versus Central Sensitization in the Pathogenesis of Pain in Chronic Pancreatitis- a Pilot and Feasibility Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Withdrawn
Why Stopped
The FDA requirements for the IND are not feasible to complete.
Study Start Date
July 1, 2021 (Actual)
Primary Completion Date
July 1, 2021 (Actual)
Study Completion Date
July 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
The major clinical features of chronic pancreatitis include glandular (exocrine and endocrine) failure and pain. Pain has remained a major clinical challenge and is present in up to 90% of patients and is the primary cause of hospitalization in most patients. Unfortunately, pain in chronic pancreatitis has been very difficult to treat.
The investigators hypothesize that the best method to reliably abolish peripheral nerve signaling is the use of a local anesthetic within the target organ (i.e. pancreas). This can best be done during endoscopic retrograde cholangiopancreatography (ERCP).
Since ERCP is done under deep sedation or general anesthesia, it is critical to select a local anesthetic whose effect persists well after recovery from the procedure; if not, the assessment of the effect of the local anesthetic on pain will be impossible to assess. The investigators have therefore chosen liposomal bupivacaine (Exparel, Pacira Pharmaceuticals), which is an FDA approved product for local infiltration that has a longer duration of action (up to 72 hours) and a slower absorption into the systemic circulation, avoiding high plasma concentrations.
Detailed Description
The major clinical features of chronic pancreatitis include glandular (exocrine and endocrine) failure and pain. The former can usually be managed satisfactorily by replacement strategies (enzymes or insulin) to restore nutritional and metabolic stability. However, pain has remained a major clinical challenge and is present in up to 90% of patients and is the primary cause of hospitalization in most patients. Unfortunately, pain in chronic pancreatitis has been very difficult to treat, and the investigators' lack of understanding about the underlying biology has led to various empirical approaches that are often based on purely anatomical grounds, and are generally highly invasive. Significant tissue injury such as that observed in chronic pancreatitis not only triggers nociceptor activation but over time, can also increase the pain in the whole system, a process called sensitization.
Determination of the contribution of peripheral versus central factors to nociceptive sensitization has significant clinical implications in an individual patient. Thus, if pain is caused primarily by signals emanating in the peripheral nerves, then perhaps invasive procedures directed against the pancreas (including pancreatectomy) are justified and can be expected to have a high probability of success. On the other hand, if central sensitization is the dominant pathophysiological factor, then these procedures may cause more harm than good and the patient may be best served using aggressive neuromodulator therapies.
The most direct way to address this question is to interrupt peripheral nerve signaling and determine how much of the pain, if any, is taken away. Unfortunately, there are no satisfactory methods to do this currently. Although celiac or splanchnic nerve blocks have been used for the treatment of pain in chronic pancreatitis, the treatments have had limited success for a variety of reasons, including the fact that the technique may not always be accurate in terms of the site of injection.
The investigators hypothesize that the best method to reliably abolish peripheral nerve signaling is the use of a local anesthetic within the target organ (i.e. pancreas). This can best be done during endoscopic retrograde cholangiopancreatography (ERCP), a technique in which the main pancreatic duct is cannulated with the help of a duodenoscope and contrast material injected. This technique is routinely done to assess pancreatic duct anatomy prior to consideration of a therapeutic intervention such as a stent, stricture dilation, or stone removal/lithotripsy.
Since ERCP is done under deep sedation or general anesthesia, it is critical to select a local anesthetic whose effect persists well after recovery from the procedure; if not, the assessment of the effect of the local anesthetic on pain will be impossible to assess. The investigators have therefore chosen liposomal bupivacaine (Exparel, Pacira Pharmaceuticals), which is an FDA approved product for local infiltration that has a longer duration of action (up to 72 hours) and a slower absorption into the systemic circulation, avoiding high plasma concentrations.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Pancreatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bupivacaine arm
Arm Type
Experimental
Arm Description
Participants undergoing ERCP as part of routine clinical care will be consented for this study.
Intervention Type
Drug
Intervention Name(s)
ERCP with Bupivacaine infusion
Intervention Description
Selective cannulation of the pancreatic duct with ERCP scope will be performed. Any contrast dye used will be carefully aspirated and the duct will be flushed with saline as necessary to clear all residual dye. The canula will be taken to the tail of the pancreatic duct, and gradually withdrawn with slow infusion of the bupivacaine solution. Liposomal bupivacaine (13.3 mg/ml of Exparel) will be injected into the main pancreatic duct for a total of 5-10 ml (depending on the length of the pancreatic duct).
Immediately after the procedure, the patient will be monitored for any evidence of acute pancreatitis (worsening abdominal pain, with amylase or lipase x3 upper limit of normal). The patient will be questioned daily after the procedure for common side effects of bupivacaine including nausea, fever, change in taste, dizziness, weakness, palpitations and loss of taste or any other new or unusual symptom.
Primary Outcome Measure Information:
Title
Change in the pain score at 24 hours after ERCP
Description
Raw pain score using a visual analog scale from 0 to 10, being 0 no pain and 10 the worst pain the participant can imagine.
Time Frame
24 hours after the ERCP
Secondary Outcome Measure Information:
Title
Change in the pain score at 2 hours after ERCP
Description
Raw pain score using a visual analog scale from 0 to 10, being 0 no pain and 10 the worst pain the participant can imagine.
Time Frame
2 hours after ERCP
Title
Change in the pain score at 48 hours after ERCP
Description
Raw pain score using a visual analog scale from 0 to 10, being 0 no pain and 10 the worst pain the participant can imagine.
Time Frame
48 hours after ERCP
Title
Change in the pain score at 72 hours after ERCP
Description
Raw pain score using a visual analog scale from 0 to 10, being 0 no pain and 10 the worst pain the participant can imagine.
Time Frame
72 hours after ERCP
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed Informed consent
Age >18 years
Patients with an established diagnosis of chronic pancreatitis with constant daily pain consistent with the same and not relieved despite standard clinical care for at least 6 months and in whom ERCP is indicated for standard of care.
Exclusion Criteria:
Significant liver or renal dysfunction.
Any Contraindication of ERCP.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pankaj Pasricha, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Hopital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Intraductal Liposomal Bupivacaine for Chronic Pancreatitis
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