Back to resultsNeurotropin to Treat Chronic Neuropathic Pain
Primary Purpose
Complex Regional Pain Syndrome Type I, Complex Regional Pain Syndrome Type II
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
Neurotropin
Sponsored by
About this trial
This is an interventional treatment trial for Complex Regional Pain Syndrome Type I focused on measuring Analgesia, Causalgia, CRPS, Neuropathic Pain, Oral Surgery, Reflex Sympathetic Dystrophy, Sympathetic Nervous System, Chronic Regional Pain Syndrome
Eligibility 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.
Sites / Locations
- National Institutes of Health Clinical Center, 9000 Rockville Pike
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Placebo first, then Neurotropin (G-1)
Neurotropin first, then Placebo (G-2)
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT00006289
First Posted
September 21, 2000
Last Updated
August 21, 2017
Sponsor
National Institute of Nursing Research (NINR)
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)
1. Study Identification
Unique Protocol Identification Number
NCT00006289
Brief Title
Neurotropin to Treat Chronic Neuropathic Pain
Official Title
Neurotropin for Acute Dental Pain and for Chronic Neuropathic Pain
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Terminated
Why Stopped
difficulty in the recruitment of patients
Study Start Date
September 2000 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Nursing Research (NINR)
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)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Complex Regional Pain Syndrome Type I, Complex Regional Pain Syndrome Type II
Keywords
Analgesia, Causalgia, CRPS, Neuropathic Pain, Oral Surgery, Reflex Sympathetic Dystrophy, Sympathetic Nervous System, Chronic Regional Pain Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo first, then Neurotropin (G-1)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Neurotropin first, then Placebo (G-2)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Drug A
Intervention Description
4 tabs b.i.d.
Intervention Type
Drug
Intervention Name(s)
Neurotropin
Other Intervention Name(s)
Drug B
Intervention Description
4 tabs b.i.d.
Primary Outcome Measure Information:
Title
Visual Analogue Scale (VAS) of Pain Scores After Administration of Test Drugs (Placebo or Neurotropin )
Description
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.
Time Frame
VAS of each patient is measured after each 5-week treatment interval with placebo or Neurotropin.
Title
Numeric Rating Scale (NRS) of Pain Scores After Administration of Test Drugs (Neurotropin or Placebo)
Description
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.
Time Frame
NRS of each patient is measured after each five-week treatment interval with placebo or Neurotropin.
Title
McGill Pain Questionnaire (MPQ) of Scores After Administration of Test Drugs (Neurotropin or Placebo)
Description
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.
Time Frame
MPQ of each patient is measured after each five-week treatment interval with drug A or drug B.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leorey Saligan, PhD, CRNP
Organizational Affiliation
National Institute of Nursing Research (NINR)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
8577483
Citation
Stanton-Hicks M, Janig W, Hassenbusch S, Haddox JD, Boas R, Wilson P. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain. 1995 Oct;63(1):127-133. doi: 10.1016/0304-3959(95)00110-E.
Results Reference
background
PubMed Identifier
9535313
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. doi: 10.1097/00002508-199803000-00007.
Results Reference
background
PubMed Identifier
10353502
Citation
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. doi: 10.1016/s0304-3959(99)00011-1.
Results Reference
background
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Neurotropin to Treat Chronic Neuropathic Pain
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