This study will examine the effectiveness of the drug neurotropin in treating chronic pain
after injury to a limb or a large nerve.
Two groups of patients will participate in this study: patients with complex regional pain
syndrome type 1, or CRPS-I (also called reflex sympathetic dystrophy) and patients with
complex regional pain syndrome type 2, or CRPS-II. CRPS-I is pain that develops after
relatively minor injury to an arm or leg, but lasts much longer and is much more severe than
would normally be expected. CRPS-II is pain resulting from injury to a large nerve.
Candidates will have a history and physical examination, blood tests, and electrocardiogram.
Participants will undergo the following tests and procedures:
Patients with CRPS I and II will receive an individualized regimen of physical therapy and
standard treatment to control their pain. In addition, they will receive neurotropin or
placebo tablets for 5 weeks, then no trial medicine for at least 1 week, and then the other
trial drug for the next 5 weeks. That is, patients who took placebo the first 5 weeks will
take neurotropin the second 5 weeks and vice versa. Neither the patients nor the doctors will
know who received which drug during the two intervals until the study is over. Patients will
complete questionnaires about their pain, quality of life, and ability to perform daily
living activities. They will have various tests to measure pain (such as sensitivity to heat
and cold, to an electric current, to a mild pin prick, etc.); to provide information about
changes in their condition (such as tests of range of motion of joints and limb size); to
measure blood circulation and sweating in the arm or leg (such as measurements of blood flow
to the limb, skin temperature, and sweat production), and other procedures.
Patients with Reflex Sympathetic Dystrophy (RSD), re-named Complex Regional Pain Syndrome,
type I (CRPS-I), have chronic, post-traumatic pain that spreads beyond the distribution of
any single peripheral nerve without evidence of major peripheral nerve damage. A similar
disorder, Causalgia, re-named CRPS-II, presents with clear evidence of nerve injury. No
successful drug treatment exists for these disorders. Neurotropin is a non-protein extract of
cutaneous tissue from rabbits inoculated with vaccinia virus. Neurotropin has been used
extensively in Japan to treat RSD and other painful conditions; however, the drug has not
undergone clinical therapeutic testing in the United States. This protocol is to carry out
double-blind, placebo-controlled, crossover studies about clinical efficacy of Neurotropin
for acute pain in dental outpatients and for chronic pain in outpatients with CRPS-I or II.
- INCLUSION CRITERIA:
CRPS patients are referred with a diagnosis of CRPS-I or CRPS-II in one limb only, based on
pain (1) that is post-traumatic and spread beyond the region of the injury; (2) has
persisted for more than 2 weeks; and (3) is associated with swelling, altered skin color or
skin temperature, altered sweating, allodynia or hyperesthesia or limitation of active
movement. Atrophic changes in skin, hair loss or nail changes, or disuse atrophy of
skeletal muscle may be present.
Both sexes are to be studied.
All ethnic and racial groups can participate.
Patients must be willing to return to NIH for follow-up evaluation under this protocol.
Pregnant and lactating women are excluded.
Based on the oral surgeon's postoperative diagnosis, any extraction which is classified as
producing unusual surgical trauma will result in exclusion from the remainder of the study.
Dental subjects will also be excluded if they are not adequately sedated by midazolam alone
and require intraoperative administration of an opioid drug such as fentanyl,
administration of greater than 14.4 ml of local anesthetic (2% lidocaine with 1:100,000
epinephrine), or postoperative administration of a steroid for possible injury to the
inferior alveolar nerve.
Patients referred with CRPS-I or CRPS II who have abnormal screening test results or who
have non-traumatic disorders to which pain may be attributed (gout, malignancy, arthritis,
etc.) will be excluded.
Any patients who have had ablative procedures for treatment of their neuropathic pain
disorder will not be eligible for inclusion in this study.
Patients who have a positive HIV result will be excluded.
Subjects with obviously impaired mental capacity that precludes informed consent and
ability to provide adequate self-ratings are to be excluded.