The effect of pregabalin treatment on patients with chronic pancreatitis
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy parameter to be evaluated is pain relief. In the clinical
part of the study the effect is assessed as changes in the daily experience of
pain, which will be assessed using questionnaires, including the modified brief
pain inventory-short form (mBPI-sf), the painDETECT questionnaire and patient
global impression of change.
In the experimental part the analgesic effect is assessed as changes in the
experimental endpoints (i.e. QST parameters). All changes are compared to
baseline recordings.
Secondary outcome
Secondary efficacy parameters are changes in quality of life compared to
baseline level. The European Organization for research and treatment of cancer
quality of life questionnaire, will be used. Also the tolerability of the drug
in this patient population will be compared to placebo.
In the experimental part of the study the slope of the QST stimulus response
curves are considered secondary efficacy parameters. The experimental baseline
recordings will also be compared to recordings from healthy controls to
evaluate general aspects of pain processing in the patient group.
Background summary
Pain by chronic pancreatitis is hard to treat. For the treatment are different
medical and surgical options.
The best attempt to establish clear guidelines for the treatment of chronic
pancreatitis is *American Gastroenterological Association Medical Position
Statement: Treatment of Pain in Chronic Pancreatitis*. Initial treatment
consists of low fat diet and non-narcotic analgesics, which can be supplemented
by oral pancreatic enzymes and proton pump inhibitors. If an acceptable level
of pain relief is not obtained with these drugs, only opioids remain for the
management of pain. Opioids have a number of well-known adverse effects and
many patients suffering from chronic pancreatitis have a history of alcoholic
abuse making opioids, with their associated abuse potential, less suitable for
these patients.
Alternatives to medical treatment exist in the form of nerve blockade,
lithotripsy and surgical treatment. However, a considerable part of patients
are not suitable for these therapies or their pain returns after medical
therapy. Thus the importance of identifying potential new treatment regimes for
the treatment of pain in chronic pancreatitis is clear.
Pregabalin is an anti-epileptic and is an analogue of the GABA
neurotransmitter. Though the exact working mechanism still needs to be
resolved, pregabalin reduces the neuronal sensitivity by binding to an
auxiliary subunit (α2-δ) of tension depend calcium channels on central neurons,
it works anti-convulsive, analgesic and anxiolitic. The effective dosage is
150-600mg daily. Pregabalin hardly gives any side-effects and is a good
addition to the standard treatment of neuropathic pain. The literature
describes trials with pain relief by post-herpetic neuralgia and painful
polyneuropathies with diabetic mellitus. The influence of pregabaline on pain
with chronic pancreatitis hasn*t been described in the literature.
Study objective
The effect of pregabalin treatment on patients with chronic pancreatitis
Study design
This will be a randomized, double-blind, parallel group, placebo-controlled
study to investigate the effects of pregabalin on clinical and experimental
pain in 30 patients with chronic pancreatitis.
Intervention
During the study, the patients will be randomized to receive placebo or
pregabalin (Lyrica®). The maximum daily dose of pregabalin is 300 mg
administered twice per day. Pregabalin is titrated in 2 steps: for the first 3
days 75mg BID is administered. From Day 4 to Day 7, 150 mg BID is
administered. From Day 8 to Day 21, 300 mg BID is administered.
If a patient does not tolerate 300mg BID it will be acceptable for them to
maintain 150mg BID for the remainder of the study, following discussion and
guidance from the investigator.
At the end of the study, patients will undertake a medication taper and will
take half their maximum tolerated daily dose of pregabalin for 7 days and then
discontinue dosing.
Study burden and risks
Side effects of pregabalin. The risks of the quantitative sensory measurements
are negligible.
Geert Grooteplein zuid 10
6500 HB Nijmegen
Nederland
Geert Grooteplein zuid 10
6500 HB Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
1. Male or female patients between the ages of 18 and 70 years with a diagnosis of chronic pancreatitis, diagnosed using the Marseille-Rome/Cambridge diagnostic criteria. Both diabetic and non-diabetic patients will be allowed to enter the study.
2. The patients must suffer from chronic abdominal pain typical for pancreatitis, meet the criteria for chronic pain (pain >/= 3 days per week in at least 3 months) and must consider their pain as severe enough for medical treatment.
3. Personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial.
4. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other trial procedures.
Exclusion criteria
1. Patients with evidence or history of medical or surgical disease of importance for this study as judged by investigator.
2. Presence or history of major depression.
3. Patients with previously diagnosed moderate to severe renal impairment. Patients with creatinine values > 2x ULN and/or with a significant change to their normal values should be excluded.
4. Patients with a screening 12-lead ECG demonstrating any of the following: heart rate >100 bpm, QRS duration >120 msec, QTc interval >450 msec, PR interval >210 msec, any clinically significant rhythm abnormality, any evidence of myocardial ischemia or injury.
5. Patients with any clinically significant laboratory abnormalities that in the opinion of the investigator may increase the risk associated with trial participation or may interfere with the interpretation of the trial results.
6. Patients treated with pregabalin (Lyrica®) during the previous 4 months.
7. Treatment with an investigational drug within 4 months preceding the first dose of study medication of importance for this study as judged by investigator.
8. Female patients who are pregnant or lactating, or intend to become pregnant. Male patients who intend to father a child during the course of the study. A pregnancy test will be conducted at visit 1 and 3 to ensure that female patients are not pregnant during the study period.
9. Patients unwilling or unable to comply with the lifestyle guidelines.
10. Patients must not suffer from painful conditions other than chronic pancreatitis.
11. Clinical significant illness within two weeks of participating in this study.
12. Involved in planning or conducting the study.
13. Hypersensitivity to pregabalin or any of its components.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-010266-28-NL |
| ClinicalTrials.gov | NCT00755573 |
| CCMO | NL25636.091.09 |