Pre-operative Pregabalin and Ketamine to Prevent Phantom Pain
| Status: | Withdrawn |
|---|---|
| Conditions: | Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 12/20/2018 |
| Start Date: | May 15, 2015 |
| End Date: | September 20, 2017 |
Effects of Pre-operative Pregabalin and Ketamine to Prevent Development of Phantom Pain in Patients Undergoing Lower Extremity Amputation
Phantom limb pain (PLP) is as painful sensations located to the missing limb and classified
as neuropathic pain. In the United States, an estimated 1.7 million patients have undergone
limb amputation, and 60% to 80% of these patients develop PLP (1-2) and it is usually
resistant to a wide variety of treatments (1-4). Three factors may contribute to the
development of persistent, post-amputation PLP by inducing central sensitization at different
times relative to surgery: pre-amputation pain, noxious intraoperative stimuli, and acute
postoperative pain (5-7).
Investigators hypothesis that pre-amputation period could be important in eliminating Phantom
Limb Pain (PLP) in the patients in whom cortical reorganization is not yet established. The
reduction of pre-operative pain and prevention of formation of pain memories may eliminate
development of PLP by using dual networks treatment strategy. This Phase III, randomized,
double-blind, placebo-controlled study is designed to evaluate the efficacy of pre-operative
pregabalin (lyrica) and ketamine in eliminating phantom limb pain in patients undergoing
lower limb amputation.
as neuropathic pain. In the United States, an estimated 1.7 million patients have undergone
limb amputation, and 60% to 80% of these patients develop PLP (1-2) and it is usually
resistant to a wide variety of treatments (1-4). Three factors may contribute to the
development of persistent, post-amputation PLP by inducing central sensitization at different
times relative to surgery: pre-amputation pain, noxious intraoperative stimuli, and acute
postoperative pain (5-7).
Investigators hypothesis that pre-amputation period could be important in eliminating Phantom
Limb Pain (PLP) in the patients in whom cortical reorganization is not yet established. The
reduction of pre-operative pain and prevention of formation of pain memories may eliminate
development of PLP by using dual networks treatment strategy. This Phase III, randomized,
double-blind, placebo-controlled study is designed to evaluate the efficacy of pre-operative
pregabalin (lyrica) and ketamine in eliminating phantom limb pain in patients undergoing
lower limb amputation.
Patients undergoing unilateral lower extremity amputation (n=30) will be randomized in this
double blind parallel placebo control clinical trial to evaluate the efficacy of
pre-operative pregabalin (lyrica) and ketamine in eliminating phantom limb pain. Patient will
receive either pregabalin and ketamine treatment (Group 1) or placebo (Group 2) during
pre-operative period approximately 4 days (2-4 days).
Patients will be identified during their anesthesia preoperative clinic or orthopedic
inpatient unit (Parkland Hospital or UT Southwestern University Hospital) for the
eligibility. Data base (EPIC) will also be used for prescreening of potential subject by
reviewing clinic visit daily schedule or operating room schedule. Then patients chart will be
reviewed for initial data collection to determine the eligibility of potential subjects with
the use of a HIPAA waiver form. Eligible subject will be approached by the study PI,
investigators, or research coordinator and written consent obtained prior to any study
procedures.
A pregnancy test will be performed before the preoperative treatment start for women in
child-bearing age: exceptions include surgically sterile women or women with medically
confirmed menopause. Women with a positive pregnancy test or who report unprotected
heterosexual sex since their previous menses or not currently using and/or willing to use a
medically approved form of contraception (e.g., birth control pill) will not enrolled to the
study.
Pain will be documented using the visual analog pain score (0=no pain, 10=worst imaginary
pain) during preoperative period before the treatment and daily on pain diary and on the day
of surgery and during postoperative period at PACU, 24 and 48 hrs. and long-term follow-up 1,
3, and 6 months after the surgery.
Total opioid dose over the 48-h study period will be documented as PCA pump morphine
consumption for postoperative first 24 hrs. and postoperative oral opioid usage for 48 hrs.
after surgery. Patients will receive a standard general anesthetic for their surgery and
postoperative standard of care pain treatment similar to all patients. Study does not limit
standard post-operative pain medication.
Long-term analgesic success will be evaluated at 1, 3, and 6 months after surgery. At
follow-up period, a pain diary will be used for the patients' self-assessment on pain
occurrence, intensity, duration for phantom and stump pain, and documentation of oral
analgesic usage. Analgesic medication use and daily pain scores will be documented on pain
diary for 1 month period following surgery. At first follow-up visit, patient will be seen in
Pain Clinic 1 month after the surgery. Patient will be called from home 3 and 6 months after
the surgery for long-term follow-up.
At all-time points, the Self-Rating Depression Scale will be used to assess depression and
the patients will complete the Pain-Related Self-Statement Scale (PRSS).
The duration of the involvement in the study will be 6 months.
Randomization:
This is randomized double-blinded placebo controlled clinical trial. Investigational Drug
Pharmacy (IDS) will randomize subjects either treatment group or placebo. IDS will dispense
the drugs/placebo.
double blind parallel placebo control clinical trial to evaluate the efficacy of
pre-operative pregabalin (lyrica) and ketamine in eliminating phantom limb pain. Patient will
receive either pregabalin and ketamine treatment (Group 1) or placebo (Group 2) during
pre-operative period approximately 4 days (2-4 days).
Patients will be identified during their anesthesia preoperative clinic or orthopedic
inpatient unit (Parkland Hospital or UT Southwestern University Hospital) for the
eligibility. Data base (EPIC) will also be used for prescreening of potential subject by
reviewing clinic visit daily schedule or operating room schedule. Then patients chart will be
reviewed for initial data collection to determine the eligibility of potential subjects with
the use of a HIPAA waiver form. Eligible subject will be approached by the study PI,
investigators, or research coordinator and written consent obtained prior to any study
procedures.
A pregnancy test will be performed before the preoperative treatment start for women in
child-bearing age: exceptions include surgically sterile women or women with medically
confirmed menopause. Women with a positive pregnancy test or who report unprotected
heterosexual sex since their previous menses or not currently using and/or willing to use a
medically approved form of contraception (e.g., birth control pill) will not enrolled to the
study.
Pain will be documented using the visual analog pain score (0=no pain, 10=worst imaginary
pain) during preoperative period before the treatment and daily on pain diary and on the day
of surgery and during postoperative period at PACU, 24 and 48 hrs. and long-term follow-up 1,
3, and 6 months after the surgery.
Total opioid dose over the 48-h study period will be documented as PCA pump morphine
consumption for postoperative first 24 hrs. and postoperative oral opioid usage for 48 hrs.
after surgery. Patients will receive a standard general anesthetic for their surgery and
postoperative standard of care pain treatment similar to all patients. Study does not limit
standard post-operative pain medication.
Long-term analgesic success will be evaluated at 1, 3, and 6 months after surgery. At
follow-up period, a pain diary will be used for the patients' self-assessment on pain
occurrence, intensity, duration for phantom and stump pain, and documentation of oral
analgesic usage. Analgesic medication use and daily pain scores will be documented on pain
diary for 1 month period following surgery. At first follow-up visit, patient will be seen in
Pain Clinic 1 month after the surgery. Patient will be called from home 3 and 6 months after
the surgery for long-term follow-up.
At all-time points, the Self-Rating Depression Scale will be used to assess depression and
the patients will complete the Pain-Related Self-Statement Scale (PRSS).
The duration of the involvement in the study will be 6 months.
Randomization:
This is randomized double-blinded placebo controlled clinical trial. Investigational Drug
Pharmacy (IDS) will randomize subjects either treatment group or placebo. IDS will dispense
the drugs/placebo.
Inclusion Criteria:
1. Ager 18-65 years old
2. Unilateral lower-limb amputations
3. Able to understand study procedures
4. If on opioids, patient should be on a stable dose for at least one week prior to
enrolment.
5. Subject with normal renal function (CrCI > 60 mL/min).
Exclusion Criteria:
1. Cases with only digits amputation
2. Current or recent history of alcohol and drug abuse
3. Concomitant use of CYP 3A4 medications
4. Unstable hypertension
5. Abnormal EKG
6. Increased intracranial pressure currently or in the past six months
7. Increased intraocular pressure currently or in the past six months
8. Liver disease or AST/ALT ≥ 3 ULN or total bilirubin >2 x ULN
9. Poorly controlled psychiatric illness.
10. A history of seizure
11. Using other anticonvulsant drug
12. Renal impairment as determined by clinically significant labs
13. Women of childbearing age who either has:
1. A positive pregnancy test
2. Unprotected heterosexual sex since their previous menses or;
3. Not currently using and/or willing to use a medically approved form of
contraception (e.g., birth control pill)
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