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Neurotropin to Treat Chronic Neuropathic Pain

This study has been terminated.
(difficulty in the recruitment of patients)
Sponsor:
Collaborators:
National Institutes of Health Clinical Center (CC)
National Institute of Neurological Disorders and Stroke (NINDS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Nursing Research (NINR) )
ClinicalTrials.gov Identifier:
NCT00006289
First received: September 21, 2000
Last updated: May 12, 2016
Last verified: May 2016
  Purpose

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.


Condition Intervention Phase
Complex Regional Pain Syndrome Type I
Complex Regional Pain Syndrome Type II
Drug: Placebo
Drug: Neurotropin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Neurotropin for Acute Dental Pain and for Chronic Neuropathic Pain

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Visual Analogue Scale (VAS) of Pain Scores After Administration of Test Drugs (Placebo or Neurotropin ) [ Time Frame: VAS of each patient is measured after each 5-week treatment interval with placebo or Neurotropin. ] [ Designated as safety issue: No ]
    Assessments of pain severity by the patient using a visual analogue scale. 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.

  • Numeric Rating Scale (NRS) of Pain Scores After Administration of Test Drugs (Neurotropin or Placebo) [ Time Frame: NRS of each patient is measured after each five-week treatment interval with placebo or Neurotropin. ] [ Designated as safety issue: No ]
    Assessments of pain severity by the patient using a numeric rating scale. 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.

  • McGill Pain Questionnaire (MPQ) of Scores After Administration of Test Drugs (Neurotropin or Placebo) [ Time Frame: MPQ of each patient is measured after each five-week treatment interval with drug A or drug B. ] [ Designated as safety issue: No ]
    Assessments of pain severity by the patient using a McGill Pain Questionnaire. 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.


Enrollment: 21
Study Start Date: September 2000
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Placebo first, then Neurotropin (G-1)
Double blind cross-over study: receive placebo for 5 weeks and then Neurotropin for 5 weeks (after at least 1 week washout period). Assignment to each group was in random order, selected by the pharmacy with all others blind.
Drug: Placebo
4 tabs b.i.d.
Other Name: Drug A
Drug: Neurotropin
4 tabs b.i.d.
Other Name: Drug B
Active Comparator: Neurotropin first, then Placebo (G-2)
Double blind cross-over study: receive Neurotropin for 5 weeks and then placebo for 5 weeks (after at least 1 week washout period). Assignment to each group was in random order, selected by the pharmacy with all others blind.
Drug: Placebo
4 tabs b.i.d.
Other Name: Drug A
Drug: Neurotropin
4 tabs b.i.d.
Other Name: Drug B

Detailed 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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006289

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Nursing Research (NINR)
National Institutes of Health Clinical Center (CC)
National Institute of Neurological Disorders and Stroke (NINDS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Leorey Saligan, PhD, CRNP National Institute of Nursing Research (NINR)
  More Information

Publications:
Responsible Party: National Institute of Nursing Research (NINR)
ClinicalTrials.gov Identifier: NCT00006289     History of Changes
Other Study ID Numbers: 000200  00-NR-0200 
Study First Received: September 21, 2000
Results First Received: June 4, 2013
Last Updated: May 12, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Analgesia
Causalgia
CRPS
Neuropathic Pain
Oral Surgery
Reflex Sympathetic Dystrophy
Sympathetic Nervous System
Chronic Regional Pain Syndrome

Additional relevant MeSH terms:
Syndrome
Neuralgia
Somatoform Disorders
Complex Regional Pain Syndromes
Reflex Sympathetic Dystrophy
Causalgia
Disease
Pathologic Processes
Pain
Neurologic Manifestations
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms
Mental Disorders
Autonomic Nervous System Diseases
Neurotropin
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on September 27, 2016