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Sickle Cell Pain: Intervention With Capsaicin Exposure (SPICE)

Primary Purpose

Neuropathic Pain, Sickle Cell Disease

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Eight Percent Topical Capsaicin

About this trial

This is an interventional treatment trial for Neuropathic Pain focused on measuring Capsaicin, Topical Analgesia, Quantitative Sensory Testing, Pain

Eligibility Criteria

14 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Children's Hospital of Michigan

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Capsaicin Arm

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

Secondary Outcome Measures

Compliance with Mobile App Record Keeping

Feasibility, as above, will be established by greater than 80 percent compliance with daily mobile app recordings of pain and home medication use.

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

Feasibility will be established by the successful processing of greater than 80 percent of target number of blood samples to be sent for hyperspectral analysis, a novel test capable of detecting chronic pain states, but not yet used in the sickle cell population.

Morphine Equivalents Utilized

Will assess changes in pain medication required during the course of the study period based on electronic medical record, participant report, and controlled substance monitoring database.

Full Information

NCT ID

NCT03899246

First Posted

January 25, 2019

Last Updated

July 27, 2020

Sponsor

Children's Hospital of Michigan

1. Study Identification

Unique Protocol Identification Number

NCT03899246

Brief Title

Sickle Cell Pain: Intervention With Capsaicin Exposure

Acronym

SPICE

Official Title

Safety and Feasibility of High-Dose Topical Capsaicin for the Treatment of Neuropathic Pain in Pediatric Sickle Cell Disease

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

July 3, 2019 (Actual)

Primary Completion Date

March 30, 2020 (Actual)

Study Completion Date

March 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Children's Hospital of Michigan

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuropathic Pain, Sickle Cell Disease

Keywords

Capsaicin, Topical Analgesia, Quantitative Sensory Testing, Pain

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Model Description

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

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Capsaicin Arm

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Eight Percent Topical Capsaicin

Other Intervention Name(s)

Qutenza

Intervention Description

See arm description

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

Compliance with Serum Substance P Levels

Description

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

Time Frame

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

Title

Compliance with Subjective Neuropathic Pain Questionnaire

Description

Time Frame

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

Title

Compliance with Quantitative Sensory Testing

Description

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.

Time Frame

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

Secondary Outcome Measure Information:

Title

Compliance with Mobile App Record Keeping

Description

Feasibility, as above, will be established by greater than 80 percent compliance with daily mobile app recordings of pain and home medication use.

Time Frame

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

Title

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

Description

Time Frame

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

Title

Morphine Equivalents Utilized

Description

Will assess changes in pain medication required during the course of the study period based on electronic medical record, participant report, and controlled substance monitoring database.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alexander K Glaros, MD

Organizational Affiliation

Children's Hospital of Michigan

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Ahmar U Zaidi, MD

Organizational Affiliation

Children's Hospital of Michigan

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Callaghan Michael, MD

Organizational Affiliation

Children's Hospital of Michigan

Official's Role

Principal Investigator

Facility Information:

Facility Name

Children's Hospital of Michigan

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Sickle Cell Pain: Intervention With Capsaicin Exposure

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