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Injecting Botulinum Toxin A Underneath the Skin to Treat Spinal Cord Pain in Patients With Spinal Cord Injury

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ClinicalTrials.gov Identifier: NCT02736890
Recruitment Status : Terminated (funding not available to continue)
First Posted : April 13, 2016
Results First Posted : April 9, 2019
Last Update Posted : April 9, 2019
Sponsor:
Information provided by (Responsible Party):
Thomas N. Bryce, Icahn School of Medicine at Mount Sinai

Brief Summary:
Back pain is a common secondary condition of both acute and chronic spinal cord injury (SCI). Current existing treatment including both pharmacologic and non-pharmacologic are limited by marginal efficacy or intolerable side effects. The purpose of this study is to evaluate the potential of subcutaneous injections of botulinum toxin A to provide pain relief in spinal cord injury patients with back pain near the level of injury in the spine. Botulinum toxin A has been shown in both pre-clinical and clinical studies to help with nerve pain. The researchers propose a double blinded placebo controlled crossover study to study the effects of subcutaneous botulinum injections to at--level SCI back pain in patients with spinal cord injury.

Condition or disease Intervention/treatment Phase
Neuropathic Back Pain Spinal Cord Injury Drug: Botulinum Toxin A Drug: Placebo Phase 2

Detailed Description:

In this study, there will be 2 procedure performed. The first procedure will be named P1 and consists of subcutaneous injection of either placebo or Botulinum Toxin A. The second procedure will be the cross-over procedure named P2. For the cross-over procedure, the subjects who had initially received Botulinum Toxin A will receive placebo and the subjects who had initially received placebo will receive Botulinum Toxin A. This is a Randomized Double-Blinded Placebo Controlled Trial. Recruited subjects will be consented, enrolled and evaluated immediately prior to P1 (or during a visit prior to the visit for P1). After the initial pre-treatment evaluation, subjects will randomly receive either placebo or Botulinum Toxin A subcutaneously (P1). A telephone follow-up (or e-mail follow up) will be performed at 2 weeks and 8 weeks post- P1. An onsite follow up will be performed 4 weeks post P1 and 12 weeks post P1.

Cross-over Study: After the 3rd month on-site evaluation (12 weeks post P1), during the same visit, the subject will proceed to the cross-over study. At this time, the patient will have the option to receive a repeat subcutaneous injection of the cross-over agent. If they desire one, a subcutaneous injection of the cross-over agent will be performed at that same visit. If they wish to defer the repeat injection, they will be contacted and asked every 4 weeks - between 12 weeks and 24 weeks post P1 (no subject will receive P2 after week 24) if they would like to have the subcutaneous injection of the cross-over agent. If they desire one, a repeat injection will be scheduled for the following week.

The rationale for a variable length of time after the initial Botulinum Toxin A/Placebo injection (P1) is to document the variability of individuals' pain response after Botulinum Toxin A. It has been reported in literature, of the subjects that respond to subcutaneous Botulinum Toxin A injections for pain, most will return to their base-line pain score in 12--24 weeks.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Subcutaneous Injection of Botulinum Toxin A for At--Level Back Pain in Patients With Spinal Cord Injury
Study Start Date : March 2016
Actual Primary Completion Date : July 17, 2018
Actual Study Completion Date : July 17, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Botulinum Toxin A
Each vial of botulin toxin (100U, BOTOX, Allergan) will be reconstituted with 4ml non-preserved saline solution (0.9%) as recommended by the manufacturer (concentration of 5 units Botulinum Toxin A/0.2ml). Each injection will be 0.2mL (BOTOX, 5 units), administered through a 25 gauge needle. The marked area will have subcutaneous injections, each separated by a radius of 1 cm, from the other injections into the marked area,(maximum of 80 injections, 400 Units).
Drug: Botulinum Toxin A
Subjects will receive subcutaneous Botulinum Toxin A injections into the marked painful region. The syringes will be prepared by a third party prior to the injection and the administrator of the procedure will be blinded to syringe content. This physician will be performing the injections under sterile conditions. Local anesthesia, EMLA (lignocaine/prilocaine eutectic mixture) cream, up to 4 grams, will be applied topically for local anesthesia. After 50 minutes, the cream will be cleaned off. Overlying skin will be sterilized with either betadine or alcohol solution.
Other Name: Botox

Placebo Comparator: Placebo
Placebo consists of 0.9% normal saline. Each injection will be 0.2mL, administered with a 25 gauge needle subcutaneously into the affected area. The marked area will have subcutaneous injections (maximum of 80) each separated from the surrounding ones by a radius of 1 cm.
Drug: Placebo
Subjects will receive subcutaneous placebo injections into the marked painful region. The syringes will be prepared by a third party prior to the injection and the administrator of the procedure will be blinded to syringe content. This physician will be performing the injections under sterile conditions. Local anesthesia, EMLA (lignocaine/prilocaine eutectic mixture) cream, up to 4 grams, will be applied topically for local anesthesia. After 50 minutes, the cream will be cleaned off. Overlying skin will be sterilized with either betadine or alcohol solution.




Primary Outcome Measures :
  1. Numeric Pain Rating Scale (NPRS) [ Time Frame: up to 12 weeks post-injection, for a total of 24 weeks from baseline ]
    Participant rated pain intensity from 0-10, with higher score indicating more pain


Secondary Outcome Measures :
  1. 7-Point Guy/Farrar Patient Global Impression of Change (PGIC) [ Time Frame: up to 12 weeks post-injection, for a total of 24 weeks from baseline ]
    Mean change from baseline. Participants are asked "Taking into account your pain level and how it affects your life, are you feeling better, the same or worse than when you started treatment?" and then to quantify the magnitude of the change. with the 7-Point guy Farrar which measures the global treatment effect from with scale from 0 to 6, higher score indicates worse outcomes.

  2. International Basic Pain Dataset - Pain Affecting Day-to-day Activities [ Time Frame: up to 12 weeks post-injection, for a total of 24 weeks from baseline ]
    The International Basic Pain Dataset is an assessment tool which includes several components including: location of pain, temporal qualities of the pain, type of pain, pain interference measures of activity, sleep, and mood. It has been shown to be valid in an interview/self -report format. The pain affecting day-to-day activities subset of the dataset is scored is from 0 to 10, with higher score indicating less favorable outcomes.

  3. International Basic Pain Dataset - Pain Affecting Mood [ Time Frame: up to 12 weeks post-injection, for a total of 24 weeks from baseline ]
    The International Basic Pain Dataset is an assessment tool which includes several components including: location of pain, temporal qualities of the pain, type of pain, pain interference measures of activity, sleep, and mood. It has been shown to be valid in an interview/self -report format. The pain affecting mood subset of the dataset is scored is from 0 to 10, with higher score indicating less favorable outcomes.

  4. International Basic Pain Dataset - Pain Affecting Sleep [ Time Frame: up to 12 weeks post-injection, for a total of 24 weeks from baseline ]
    The International Basic Pain Dataset is an assessment tool which includes several components including: location of pain, temporal qualities of the pain, type of pain, pain interference measures of activity, sleep, and mood. It has been shown to be valid in an interview/self -report format. The pain affecting sleep subset of the dataset is scored is from 0 to 10, with higher score indicating less favorable outcomes.

  5. Static Mechanical Allodynia Testing [ Time Frame: up to 12 weeks post-injection, for a total of 24 weeks from baseline ]
    Mechanical allodynia is a characteristic of evoked pain in subjects with neuropathic pain. Static allodynia to mechanical stimuli will be defined as a sensation of pain evoked by the pressure of the end of a wooden stick. The end of a wooden stick will touch the affected region with enough pressure to indent the skin, for 10 seconds. Afterwards, the subject will be asked to rate the perceived pain on an 11-point NRS.

  6. Dynamic Mechanical Allodynia Testing [ Time Frame: up to 12 weeks post-injection, for a total of 24 weeks from baseline ]
    Dynamic allodynia will be tested by stroking the affected region gently with a cotton swab, 4 times at a rate of 3-5cm per second over an area of 5cm. If there is an evoked clear sensation of pain, the subject is asked to rate the intensity of dynamic allodynia using the 11-point NRS. The region of static and dynamic allodynia, if present, will be marked and recorded

  7. Patient-generated Index (PGI) [ Time Frame: up to 12 weeks post-injection, for a total of 24 weeks from baseline ]
    PGI measures activity affected by pain. Full score is 0 to 10000, with higher score indicating better function



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Between the ages of 18 and 80 years old
  • Diagnosed with traumatic spinal cord injury
  • Target pain is considered by the physician as at-level SCI in nature to a high degree of certainty (4 or 5 using a Likert confidence scale ranging from 0-5 where 0 is "purely a guess" and 5 is "absolutely certain")
  • Able to give written informed consent
  • Target pain that has been continuously present for at least one month
  • Target pain is of at least moderate average intensity over the past week, e.g., greater than or equal to 4/10 on a numeric rating scale, the cutoff point for moderate pain in an SCI population.
  • Target pain is localized within the dermatome which identifies the NLI or within 3 levels below the NLI
  • Subject has been on a stable dose of analgesic mediation (or not on analgesic medication) for at least 3 weeks and is agreeable to remaining on current regimen for the duration of the study (previous prescribed breakthrough analgesics will be allowed)

Exclusion Criteria:

  • Pregnancy
  • History of intolerance, hypersensitivity or known allergy to botulinum toxin or its preservatives
  • History of intolerance, hypersensitivity or known allergy to EMLA cream (lignocaine/prilocaine eutectic mixture) which is used as an analgesic during BoNT injection
  • Recent history of administration of botulinum toxin (within previous 6 months)
  • Contraindications to botulinum toxin (myasthenia gravis or other disease of the neuromuscular junction)
  • Coagulation disorder
  • Current infection
  • Insufficient command of English to complete self-report instruments.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02736890


Locations
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United States, New York
Mount Sinai Hospital
New York, New York, United States, 10029
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
Investigators
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Principal Investigator: Thomas Bryce, MD Icahn School of Medicine at Mount Sinai
  Study Documents (Full-Text)

Documents provided by Thomas N. Bryce, Icahn School of Medicine at Mount Sinai:
Study Protocol  [PDF] December 29, 2015
Statistical Analysis Plan  [PDF] December 29, 2015


Publications:
Samuelsson KK. Back pain and spinal Deformity—Common among wheelchair users with spinal cord injuries. Scandinavian journal of occupational therapy. 1996 -01;3(1):28-32.
Fabregat G, Asensio-Samper JM, Palmisani S, Villanueva-Perez VL, De Andres J. Subcutaneous botulinum toxin for chronic post-thoracotomy pain. Pain Pract. 2012 Jun 21.

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Responsible Party: Thomas N. Bryce, Professor of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT02736890     History of Changes
Other Study ID Numbers: GCO 14-2212
First Posted: April 13, 2016    Key Record Dates
Results First Posted: April 9, 2019
Last Update Posted: April 9, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The following will be shared: demographic information, pain response to interventions, adverse events and functional outcomes. The above information will be obtain in the forms of questionnaires and surveys. The data will be available when the study concludes.

Keywords provided by Thomas N. Bryce, Icahn School of Medicine at Mount Sinai:
Botulinum Toxin A
Neuropathic pain
Spinal cord injury
Pain management
Rehabilitation

Additional relevant MeSH terms:
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Wounds and Injuries
Back Pain
Spinal Cord Injuries
Pain
Neurologic Manifestations
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Botulinum Toxins
Botulinum Toxins, Type A
abobotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents