"Efficacy of Botulinum Toxin Injection in Reducing Limb Pain in Patients With Complex Regional Pain Syndrome"

NCT03616262 | Unknown Early Phase 1 DMC FDA Drug

• 1 other identifier: VACHS
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: The primary aim is to evaluate the efficacy of botulinum toxin A in reducing overall limb pain in patients with complex regional pain syndrome (CRPS). Additionally the investigators would like to see if quality of life is improved and disability scores decreased. Research Design: This is a double blinded, randomized cross-over study that will be conducted over a 7 month period. It is a pilot study that will include twenty subjects recruited from the Neurology CRPS clinic at VA Connecticut and from outside VA hospitals within a 150 mile radius. Subjects will receive an intramuscular injection Treatment A which is only 1% lidocaine or Treatment B which is mixture of botulinum toxin A + 1% lidocaine in the affected limb only. This is a cross over study where patients will receive Treatment A or B initially during the first of four study visits and during the third study visit while receive whichever treatment not given during the first visit. Dr. Sameer Ali, VA neurology fellow, will be blinded when administering the treatments. Dr. Hajime Tokuno, VA neurologist who is the principal investigator of the trial will prepare the treatments. Clinical pharmacy will be randomizing the treatments. Dr. Tokuno will not be blinded as he needs to know which treatment has been given in case of complications. Impact/Significance: The significance of this study is the possible discovery of a new, safer, less invasive, and more efficacious therapeutic option for patients suffering from CRPS. Currently medical management with neuropathic pain meds, interventions such as sympathetic nerve blocks and ketamine infusion has helped some patients and not others. The investigators are trying to see whether either of the two treatments and especially the treatment with botulinum toxin may be a more viable alternative than existing modalities.

Conditions

Complex Regional Pain Syndrome

Outcome Measures

Primary Outcomes (1)

• Reduction in the VAS score will be the primary outcome measure.

  The VAS score will be obtained using the VAS at each of the four study visits. Zero is no pain and ten is maximum pain on the zero to ten scale.

  7 months

Secondary Outcomes (7)

• Quality of Life as a measure of function with pain.

  7 months

• Disability

  7 months

• Thermography

  7 months

• Goniometry

  7 months

• Algometry

  7 months

Study Arms (2)

Phase 1

ACTIVE COMPARATOR

In Phase 1, subjects will receive either Treatment A (Lidocaine alone) or Treatment B (Botox+Lidocaine )

Drug: Botox + Lidocaine; Drug: Lidocaine alone

Phase 2

ACTIVE COMPARATOR

In Phase 2, subjects will receive either Treatment B (Botox+Lidocaine) or Treatment A (Lidocaine alone) -- the opposite of what was administered in Phase 1

Drug: Botox + Lidocaine; Drug: Lidocaine alone

Interventions

Botox + Lidocaine DRUG

The total dose per patient in the lower extremity or upper extremity will be based on common doses given in spasticity patients in the neurology injection clinic. If the target is a symptomatic arm, we will inject as follows: biceps 30 units, triceps 40 units, flexor carpi radialis 20 units, extensor carpi radialis 20 units. If the target is a symptomatic leg, we will inject in the following pattern: vastus lateralis 50 units, rectus femoris 30 units, medial gastrocnemius 40 units, tibialis anterior 40 units.

Phase 1; Phase 2

Lidocaine alone DRUG

The total dose per patient in the lower extremity or upper extremity will be based on common doses given in spasticity patients in the neurology injection clinic. If the target is a symptomatic arm, we will inject as follows: biceps 30 units, triceps 40 units, flexor carpi radialis 20 units, extensor carpi radialis 20 units. If the target is a symptomatic leg, we will inject in the following pattern: vastus lateralis 50 units, rectus femoris 30 units, medial gastrocnemius 40 units, tibialis anterior 40 units.

Phase 1; Phase 2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients with documented diagnosis of CRPS per International Pain Society Guidelines. Diagnosis must be made or confirmed in the neurology CRPS clinic prior to recruitment.
• Patients ages 18-80.
• Patients may or may not have tried other therapeutics, will not affect study.
• Veterans enrolled in the Veterans Hospital system of the United States.
• Patients enrolled either type I or II CRPS of either upper or lower extremity.

You may not qualify if:

• Prior history of adverse side effects with use of botulinum toxin.
• Prior adverse reaction to lidocaine use.
• CRPS involving multiple extremities.
• Myasthenia gravis, myopathy, severe polyneuropathy or other causes of chronic muscle weakness.
• History of severe mental illness or dementia.

Sponsors & Collaborators

• VA Connecticut Healthcare System: lead
• Allergan: collaborator

Study Sites (1)

VA Connecticut Healthcare System

West Haven, Connecticut, 06854, United States

RECRUITING

Related Publications (13)

• Argoff CE. A focused review on the use of botulinum toxins for neuropathic pain. Clin J Pain. 2002 Nov-Dec;18(6 Suppl):S177-81. doi: 10.1097/00002508-200211001-00010.

  PMID: 12569966 BACKGROUND

• Birthi P, Sloan P, Salles S. Subcutaneous botulinum toxin A for the treatment of refractory complex regional pain syndrome. PM R. 2012 Jun;4(6):446-9. doi: 10.1016/j.pmrj.2011.12.010. No abstract available.

  PMID: 22732156 BACKGROUND

• Borchers AT, Gershwin ME. Complex regional pain syndrome: a comprehensive and critical review. Autoimmun Rev. 2014 Mar;13(3):242-65. doi: 10.1016/j.autrev.2013.10.006. Epub 2013 Oct 23.

  PMID: 24161450 BACKGROUND

• Choi E, Lee PB, Nahm FS. Interexaminer reliability of infrared thermography for the diagnosis of complex regional pain syndrome. Skin Res Technol. 2013 May;19(2):189-93. doi: 10.1111/srt.12032. Epub 2013 Jan 20.

  PMID: 23331254 BACKGROUND

• Chen S. Clinical uses of botulinum neurotoxins: current indications, limitations and future developments. Toxins (Basel). 2012 Oct;4(10):913-39. doi: 10.3390/toxins4100913. Epub 2012 Oct 19.

  PMID: 23162705 BACKGROUND

• Jeong MY, Yu JS, Chung WB. Usefulness of thermography in diagnosis of complex regional pain syndrome type I after transradial coronary intervention. J Invasive Cardiol. 2013 Sep;25(9):E183-5.

  PMID: 23995728 BACKGROUND

• Kalandakanond S, Coffield JA. Cleavage of SNAP-25 by botulinum toxin type A requires receptor-mediated endocytosis, pH-dependent translocation, and zinc. J Pharmacol Exp Ther. 2001 Mar;296(3):980-6.

  PMID: 11181932 BACKGROUND

• Niehof SP, Huygen FJ, Stronks DL, Klein J, Zijlstra FJ. Reliability of observer assessment of thermographic images in complex regional pain syndrome type 1. Acta Orthop Belg. 2007 Feb;73(1):31-7.

  PMID: 17441655 BACKGROUND

• Niehof SP, Beerthuizen A, Huygen FJ, Zijlstra FJ. Using skin surface temperature to differentiate between complex regional pain syndrome type 1 patients after a fracture and control patients with various complaints after a fracture. Anesth Analg. 2008 Jan;106(1):270-7, table of contents. doi: 10.1213/01.ane.0000289635.95869.70.

  PMID: 18165590 BACKGROUND

• Ra JY, An S, Lee GH, Kim TU, Lee SJ, Hyun JK. Skin temperature changes in patients with unilateral lumbosacral radiculopathy. Ann Rehabil Med. 2013 Jun;37(3):355-63. doi: 10.5535/arm.2013.37.3.355. Epub 2013 Jun 30.

  PMID: 23869333 BACKGROUND

• Safarpour D, Jabbari B. Botulinum toxin A (Botox) for treatment of proximal myofascial pain in complex regional pain syndrome: two cases. Pain Med. 2010 Sep;11(9):1415-8. doi: 10.1111/j.1526-4637.2010.00929.x. Epub 2010 Aug 23.

  PMID: 20735753 BACKGROUND

• Safarpour D, Salardini A, Richardson D, Jabbari B. Botulinum toxin A for treatment of allodynia of complex regional pain syndrome: a pilot study. Pain Med. 2010 Sep;11(9):1411-4. doi: 10.1111/j.1526-4637.2010.00897.x. Epub 2010 Jun 30.

  PMID: 20609130 BACKGROUND

• Shahidi B, Johnson CL, Curran-Everett D, Maluf KS. Reliability and group differences in quantitative cervicothoracic measures among individuals with and without chronic neck pain. BMC Musculoskelet Disord. 2012 Oct 31;13:215. doi: 10.1186/1471-2474-13-215.

  PMID: 23114092 BACKGROUND

MeSH Terms

Conditions

Complex Regional Pain Syndromes

Interventions

Botulinum Toxins, Type A; Lidocaine

Condition Hierarchy (Ancestors)

Autonomic Nervous System Diseases; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Central Study Contacts

Sameer S Ali, MD

CONTACT

2032471860; sameer.ali@sluhn.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2015
• First Posted: August 6, 2018
• Study Start: July 1, 2016
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: August 6, 2018

Record last verified: 2018-07

Locations

US (1)