Neurotropin to Treat Chronic Neuropathic Pain

Complex Regional Pain Syndrome Type I Clinical Trial

Official title:

Neurotropin for Acute Dental Pain and for Chronic Neuropathic Pain

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00006289
• Other study ID #: 000200
• Secondary ID: 00-NR-0200
• Status: Terminated
• Phase: Phase 2
• First received: September 21, 2000
• Last updated: August 21, 2017
• Start date: September 2000
• Est. completion date: June 2012

Study information

• Verified date: August 2017
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• 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.

EXCLUSION CRITERIA:

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.

Related Conditions & MeSH terms

• Causalgia
• Complex Regional Pain Syndrome Type I
• Complex Regional Pain Syndrome Type II
• Complex Regional Pain Syndromes
• Neuralgia
• Reflex Sympathetic Dystrophy
• Somatoform Disorders
• Syndrome

Intervention

Drug:
• Placebo
4 tabs b.i.d.
• Neurotropin
4 tabs b.i.d.

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (4)

Lead Sponsor	Collaborator
National Institute of Nursing Research (NINR)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health Clinical Center (CC)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Bruehl S, Harden RN, Galer BS, Saltz S, Bertram M, Backonja M, Gayles R, Rudin N, Bhugra MK, Stanton-Hicks M. External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria. International Association for the Study of Pain. Pain. 1999 May;81(1-2):147-54. — View Citation

Galer BS, Bruehl S, Harden RN. IASP diagnostic criteria for complex regional pain syndrome: a preliminary empirical validation study. International Association for the Study of Pain. Clin J Pain. 1998 Mar;14(1):48-54. — View Citation

Stanton-Hicks M, Jänig W, Hassenbusch S, Haddox JD, Boas R, Wilson P. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain. 1995 Oct;63(1):127-33. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual Analogue Scale (VAS) of Pain Scores After Administration of Test Drugs (Placebo or Neurotropin )	Assessments of pain severity by the patient using a visual analogue scale ranging from 0 to 100 (mm), with 0 = no pain and 100 = maximal pain level. When it is difficult to recruit the patients, the interim analysis using these data is performed after completion of the study of first 16 patients (target number is 30). The data from 16 patients was analyzed while investigators were blinded to the treatment code (Drug A and B) provided by the NIH pharmacy. Only after the analysis was completed was the code unblinded. Placebo or Neurotropin" in place of "drug A or drug B.	VAS of each patient is measured after each 5-week treatment interval with placebo or Neurotropin.
Primary	Numeric Rating Scale (NRS) of Pain Scores After Administration of Test Drugs (Neurotropin or Placebo)	Assessments of pain severity by the patient using a numeric rating scale ranging from 0 to 10 as a verbal response where 0 = no pain and 10 =maximal pain. When it is difficult to recruit the patients, the interim analysis using these data is performed after completion of the study of first 16 patients (target number is 30). The data from 16 patients was analyzed while the investigators are blinded to the treatment code (Drug A or B) provided by the NIH pharmacy. Only after the analysis was completed was the code unblinded. Placebo or Neurotropin" in place of "drug A or drug B.	NRS of each patient is measured after each five-week treatment interval with placebo or Neurotropin.
Primary	McGill Pain Questionnaire (MPQ) of Scores After Administration of Test Drugs (Neurotropin or Placebo)	Assessments of pain severity by the patient using a McGill Pain Questionnaire which consists of 3 major classes of word descriptors-sensory, affective and evaluative - that are used by patients to specify subjective pain experience. Each word chosen from descriptor responses to 20 questions is given a value and the sum of the values of the responses provides a score which is an index of the pain severity with a minimum value of 20 and a maximal value of 78. When it is difficult to recruit the patients, the interim analysis using these data is performed after completion of the study of first 16 patients (target number is 30). The data from 16 patients was analyzed while investigators are blinded to the treatment code (drug A or B) provided by the NIH pharmacy. Only after the analysis was completed was the code unblinded. Placebo or Neurotropin" in place of "drug A or drug B.	MPQ of each patient is measured after each five-week treatment interval with drug A or drug B.