Sickle Cell Pain: Intervention With Capsaicin Exposure
Sickle Cell Pain: Intervention With Capsaicin Exposure
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.
Patients with sickle cell disease suffer debilitating painful episodes, as well as chronic,
 often daily, pain that are commonly treated with non-steroidal anti-inflammatory drugs,
 opioids, and other non-pharmacologic supportive measures. Neuropathic pain has been shown to
 be present in these patients, with frequency increasing with age. It is believed, based on
 knowledge of neuropathic pain related to other conditions and from the small number of
 studies in sickle cell patients, to result from repeated vaso-occlusive pain episodes that
 prime central and peripheral pain sensing pathways in a maladaptive manner, leading to
 hyper-sensitization. Very few studies to date have evaluated therapies specifically targeting
 this aspect of the pain experienced by patients with sickle cell disease.

 This is a pilot study for a future longitudinal study of neuropathic pain in pediatric
 patients with sickle cell disease. The first aim of this pilot study is to establish the
 safety of treating participants with sickle cell disease aged fourteen to twenty-one with
 eight percent topical capsaicin patches on an every three-month dosing schedule as
 recommended by the manufacturer. This will be a single-arm safety study. Presence of
 neuropathic pain will be determined by day zero evaluation via the testing shown in the
 outcome measures below. Topical medication will be administered over one hour, every three
 months, for six months (total of three applications), to sites of recurrent vaso-occlusive
 pain, according to the package insert administration guidelines. Subjective and objective
 evaluations of pain and inflammation including questionnaires, blood tests, and quantitative
 sensory testing will be carried out every six weeks throughout the study period until twelve
 weeks after the final capsaicin application. Additionally, participants will record daily
 pain and medication use in a mobile app. Safety will be established by there being no grade
 three or four adverse events according to CTCAE definitions. Grade two adverse events will be
 evaluated on a case by case basis throughout the duration of the study. Feasibility of
 monitoring neuropathic pain with the aforementioned studies will be established by
 participant compliance with greater than eighty percent of all study activities.
Inclusion Criteria:

 -  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.

 Exclusion Criteria:

 -  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.