Sickle Cell Pain: Intervention With Capsaicin Exposure

NCT03899246 | Completed Phase 1 FDA Drug

• 1 other identifier: SPICE1.0
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the safety and feasibility of using high dose topical capsaicin patches for the treatment of neuropathic pain in pediatric patients with sickle cell disease, as well as the feasibility of using a number of tests for the evaluation and monitoring of neuropathic pain. The hypothesis, based on evidence obtained from studies in adults with neuropathic pain related to other diseases as well as a single previously published study of capsaicin in pediatric patients, is that capsaicin will be well tolerated in this population. Additionally, it is hypothesized that it is feasible to monitor changes in neuropathic pain via the testing listed below.

Conditions

Neuropathic Pain; Sickle Cell Disease

Keywords

Capsaicin; Topical Analgesia; Quantitative Sensory Testing; Pain

Outcome Measures

Primary Outcomes (4)

• Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE Criteria

  Safety will be established by there being no treatment-related adverse events greater than grade 2 using CTCAE definitions of adverse events. Grade 2 CTCAE events will be evaluated on a case by case basis to determine safety of continuing the study. Grade 3 events will result in immediate suspension of study activities until a full analysis of the event in question is completed.

  At the end of the 9 month study period all participant information will be reviewed and adverse events assessed.

• Compliance with Serum Substance P Levels

  Feasibility will be established by participants having greater than 80 percent compliance with all study investigations, including serum substance P levels.

  At the end of the 9 month study period all participant information will be reviewed and compliance with testing assessed.

• Compliance with Subjective Neuropathic Pain Questionnaire

  Feasibility will be established by participants having greater than 80 percent compliance with all study investigations, including completion of PainDETECT Questionnaire during study visits. The questionnaire is a validated assessment of neuropathic pain. It consists of a series of questions regarding the experience of pain for which the participant will provide an answer ranging from "never" (0 points) to "very strongly" (5 points). Points are added to provide a total score from 0 to 38. A score from 0 to 12 indicates a neuropathic pain component is unlikely, a score of 12 to 18 is equivocal, and a score greater than 18 indicates a neuropathic component is likely.

  At the end of the 9 month study period all participant information will be reviewed and compliance with testing assessed.

• Compliance with Quantitative Sensory Testing

  Feasibility will be established by participants having greater than 80 percent compliance with all study investigations, including quantitative sensory testing using electronic von frey machine.

  At the end of the 9 month study period all participant information will be reviewed and compliance with testing assessed.

Secondary Outcomes (3)

• Compliance with Mobile App Record Keeping

  Duration of study period (9 months). Mobile app recordings can be reviewed in real time and will be recorded on a weekly basis.

• Compliance with Blood Draws for Hyperspectral Imaging Analysis for Determining Presence and Improvement of Chronic Neuropathic Pain

  Duration of study period (9 months). Will be drawn and processed at 6 week intervals throughout the study period.

• Morphine Equivalents Utilized

  Duration of study period (9 months). Will be evaluated at 6 week intervals throughout the study period.

Study Arms (1)

Capsaicin Arm

EXPERIMENTAL

Single arm to receive eight percent topical capsaicin applied to up to 4 sites of recurrent pain over one hour on an every three month schedule. Participants in this arm will receive pretreatment with topical five percent lidocaine.

Drug: Eight Percent Topical Capsaicin

Interventions

Eight Percent Topical Capsaicin DRUG

See arm description

Also known as: Qutenza

Capsaicin Arm

Eligibility Criteria

• Age: 14 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• A diagnosis of either Sickle Cell Disease with genotype SS or S Beta-zero, or SC disease.
• Must have recurrent sites of pain, where majority of acute pain episodes are localized
• Subjects are willing and able to comply with scheduled visits, treatment plan, laboratory tests, pain assessments, and other study procedures.
• Subjects who are being treated with hydroxyurea (HU) must have been on a stable dose for at least 8 weeks prior to Visit 1 (Day 0), with the intent of remaining on the same dose of hydroxyurea throughout the clinical trial including the protocol-specified follow-up period unless adjustments are medically necessary due to bone marrow suppression.
• At least 80% compliance (defined as logging pain at least once daily) with mobile application use during 14-day lead in period from time of enrollment to time of first capsaicin application.

You may not qualify if:

• Age less than 14 or greater than 21
• History of major surgery within the past 3 months.
• Patients receiving scheduled chronic partial exchange transfusions as part of their sickle cell disease management protocol.
• Concurrently taking another medication used in the treatment of neuropathic pain or with the potential to affect the peripheral nervous system (e.g. gabapentin, anti-epileptics, antidepressants, systemic alpha or beta adrenergic receptor blockers)
• Use of another topical analgesic at home in the treatment of pain episodes such as topical lidocaine, diclofenac, or menthol (must discontinue use at the time of enrollment).
• Recurrent pain secondary to an underlying condition other than vaso-occlusive pain (avascular necrosis, scoliosis, fracture, etc.)
• Patients lacking the mental capacity to assent to the study
• Patients with another chronic inflammatory/immune disorder that could skew the inflammatory markers listed above.
• Pregnant females
• Expectation that the subject will not be able to be followed for the duration of the study
• Active use of illicit drugs and/or alcohol dependence, as determined by the investigator. Opioid use beyond the amount necessary for pain related to the underlying sickle cell disease as determined by the investigator.
• Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator.

Sponsors & Collaborators

• Children's Hospital of Michigan: lead

Study Sites (1)

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Related Publications (24)

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  PMID: 15712781 BACKGROUND

• Franck LS, Treadwell M, Jacob E, Vichinsky E. Assessment of sickle cell pain in children and young adults using the adolescent pediatric pain tool. J Pain Symptom Manage. 2002 Feb;23(2):114-20. doi: 10.1016/s0885-3924(01)00407-9.

  PMID: 11844631 BACKGROUND

• Brandow AM, Farley RA, Panepinto JA. Neuropathic pain in patients with sickle cell disease. Pediatr Blood Cancer. 2014 Mar;61(3):512-7. doi: 10.1002/pbc.24838. Epub 2013 Oct 26.

  PMID: 24167104 BACKGROUND

• Brandow AM, Zappia KJ, Stucky CL. Sickle cell disease: a natural model of acute and chronic pain. Pain. 2017 Apr;158 Suppl 1(Suppl 1):S79-S84. doi: 10.1097/j.pain.0000000000000824. No abstract available.

  PMID: 28221286 BACKGROUND

• Antunes FD, Propheta VGS, Vasconcelos HA, Cipolotti R. Neuropathic pain in patients with sickle cell disease: a cross-sectional study assessing teens and young adults. Ann Hematol. 2017 Jul;96(7):1121-1125. doi: 10.1007/s00277-017-2984-z. Epub 2017 Mar 30.

  PMID: 28361297 BACKGROUND

• Brandow AM, Farley RA, Panepinto JA. Early insights into the neurobiology of pain in sickle cell disease: A systematic review of the literature. Pediatr Blood Cancer. 2015 Sep;62(9):1501-11. doi: 10.1002/pbc.25574. Epub 2015 May 13.

  PMID: 25976161 BACKGROUND

• Kenyon N, Wang L, Spornick N, Khaibullina A, Almeida LE, Cheng Y, Wang J, Guptill V, Finkel JC, Quezado ZM. Sickle cell disease in mice is associated with sensitization of sensory nerve fibers. Exp Biol Med (Maywood). 2015 Jan;240(1):87-98. doi: 10.1177/1535370214544275. Epub 2014 Jul 28.

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• Garrison SR, Kramer AA, Gerges NZ, Hillery CA, Stucky CL. Sickle cell mice exhibit mechanical allodynia and enhanced responsiveness in light touch cutaneous mechanoreceptors. Mol Pain. 2012 Sep 10;8:62. doi: 10.1186/1744-8069-8-62.

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• Henrich F, Magerl W, Klein T, Greffrath W, Treede RD. Capsaicin-sensitive C- and A-fibre nociceptors control long-term potentiation-like pain amplification in humans. Brain. 2015 Sep;138(Pt 9):2505-20. doi: 10.1093/brain/awv108. Epub 2015 May 4.

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  PMID: 20021438 BACKGROUND

• Jessell TM. Substance P in nociceptive sensory neurons. Ciba Found Symp. 1982;(91):225-48. doi: 10.1002/9780470720738.ch13.

  PMID: 6183072 BACKGROUND

• Yaksh TL, Farb DH, Leeman SE, Jessell TM. Intrathecal capsaicin depletes substance P in the rat spinal cord and produces prolonged thermal analgesia. Science. 1979 Oct 26;206(4417):481-3. doi: 10.1126/science.228392.

  PMID: 228392 BACKGROUND

• Jessell TM, Iversen LL, Cuello AC. Capsaicin-induced depletion of substance P from primary sensory neurones. Brain Res. 1978 Aug 18;152(1):183-8. doi: 10.1016/0006-8993(78)90146-4. No abstract available.

  PMID: 209869 BACKGROUND

• Simone DA, Nolano M, Johnson T, Wendelschafer-Crabb G, Kennedy WR. Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci. 1998 Nov 1;18(21):8947-59. doi: 10.1523/JNEUROSCI.18-21-08947.1998.

  PMID: 9787000 BACKGROUND

• Nolano M, Simone DA, Wendelschafer-Crabb G, Johnson T, Hazen E, Kennedy WR. Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation. Pain. 1999 May;81(1-2):135-45. doi: 10.1016/s0304-3959(99)00007-x.

  PMID: 10353501 BACKGROUND

• Kennedy WR, Vanhove GF, Lu SP, Tobias J, Bley KR, Walk D, Wendelschafer-Crabb G, Simone DA, Selim MM. A randomized, controlled, open-label study of the long-term effects of NGX-4010, a high-concentration capsaicin patch, on epidermal nerve fiber density and sensory function in healthy volunteers. J Pain. 2010 Jun;11(6):579-87. doi: 10.1016/j.jpain.2009.09.019. Epub 2010 Apr 18.

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• Burness CB, McCormack PL. Capsaicin 8 % Patch: A Review in Peripheral Neuropathic Pain. Drugs. 2016 Jan;76(1):123-34. doi: 10.1007/s40265-015-0520-9.

  PMID: 26666418 BACKGROUND

• Rodriguez-Lopez MJ, Fernandez-Baena M, Barroso A, Yanez-Santos JA. Complex Regional Pain Syndrome in Children: a Multidisciplinary Approach and Invasive Techniques for the Management of Nonresponders. Pain Pract. 2015 Nov;15(8):E81-9. doi: 10.1111/papr.12317. Epub 2015 Jun 11.

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• Brandow AM, Wandersee NJ, Dasgupta M, Hoffmann RG, Hillery CA, Stucky CL, Panepinto JA. Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use. Br J Haematol. 2016 Oct;175(2):237-245. doi: 10.1111/bjh.14300. Epub 2016 Aug 19.

  PMID: 27539682 BACKGROUND

• Kuei N, Patel N, Xu H, et al. Characteristics and Potential Biomarkers for Chronic Pain in Patients with Sickle Cell Disease. Blood. 2015;126(23). http://www.bloodjournal.org/content/126/23/986?utm_source=TrendMD&utm_medium=cpc&utm_campaign=Blood_TrendMD_0&sso-checked=true. Accessed July 7, 2018.

  BACKGROUND

• O'Leary JD, Crawford MW, Odame I, Shorten GD, McGrath PA. Thermal pain and sensory processing in children with sickle cell disease. Clin J Pain. 2014 Mar;30(3):244-50. doi: 10.1097/AJP.0b013e318292a38e.

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• Brandow AM, Panepinto JA. Clinical Interpretation of Quantitative Sensory Testing as a Measure of Pain Sensitivity in Patients With Sickle Cell Disease. J Pediatr Hematol Oncol. 2016 May;38(4):288-93. doi: 10.1097/MPH.0000000000000532.

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• Staikopoulos V, Gosnell ME, Anwer AG, Mustafa S, Hutchinson MR, Goldys EM. Hyperspectral imaging of endogenous fluorescent metabolic molecules to identify pain states in central nervous system tissue. In: Hutchinson MR, Goldys EM, eds. Vol 10013. International Society for Optics and Photonics; 2016:1001306. doi:10.1117/12.2243158

  BACKGROUND

MeSH Terms

Conditions

Neuralgia; Anemia, Sickle Cell; Pain

Interventions

Capsaicin

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Polyunsaturated Alkamides; Amides; Organic Chemicals; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids

Study Officials

• Alexander K Glaros, MD

  Children's Hospital of Michigan

  PRINCIPAL INVESTIGATOR

• Ahmar U Zaidi, MD

  Children's Hospital of Michigan

  PRINCIPAL INVESTIGATOR

• Callaghan Michael, MD

  Children's Hospital of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Hematology-Oncology Fellow

Model Details: Single arm, safety and feasibility trial assessing the suitability of an FDA approved medication for use in children with an off-label condition.

Study Record Dates

• First Submitted: January 25, 2019
• First Posted: April 2, 2019
• Study Start: July 3, 2019
• Primary Completion: March 30, 2020
• Study Completion: March 30, 2020
• Last Updated: July 29, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)