Neurotropin to Treat Chronic Neuropathic Pain

NCT00006289 | Terminated Phase 2 Results

• 2 other identifiers: 00020000-NR-0200
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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.

• 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.

• 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.

Study Arms (2)

Placebo first, then Neurotropin (G-1)

ACTIVE COMPARATOR

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; Drug: Neurotropin

Neurotropin first, then Placebo (G-2)

ACTIVE COMPARATOR

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; Drug: Neurotropin

Interventions

Placebo DRUG

4 tabs b.i.d.

Also known as: Drug A

Neurotropin first, then Placebo (G-2); Placebo first, then Neurotropin (G-1)

Neurotropin DRUG

4 tabs b.i.d.

Also known as: Drug B

Neurotropin first, then Placebo (G-2); Placebo first, then Neurotropin (G-1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Pregnant and lactating women are excluded.
• 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.
• 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.

Sponsors & Collaborators

• National Institute of Nursing Research (NINR): lead
• National Institutes of Health Clinical Center (CC): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 8577483 BACKGROUND

• 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.

  PMID: 9535313 BACKGROUND

• 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.

  PMID: 10353502 BACKGROUND

MeSH Terms

Conditions

Complex Regional Pain Syndromes; Causalgia; Agnosia; Neuralgia; Reflex Sympathetic Dystrophy

Interventions

neurotropin

Condition Hierarchy (Ancestors)

Autonomic Nervous System Diseases; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pain

Limitations and Caveats

Because of the difficulty in patient recruitment, the interim analysis was performed for the first 16 patients (target was 30). The results are inconclusive due to large variations in pain scores associated with insufficient the number of patients.

Results Point of Contact

• Title: Dr. Leorey Saligan (Principal Investigator, former PI: Dr. Raymond Dioone)
• Organization: National Institute of Nursing Research

saliganl@mail.nih.gov

301-451-1685

Study Officials

• Leorey Saligan, PhD, CRNP

  National Institute of Nursing Research (NINR)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2000
• First Posted: September 22, 2000
• Study Start: September 1, 2000
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: August 22, 2017
• Results First Posted: June 21, 2016

Record last verified: 2017-08

Locations

US (1)