Clinical trial NCT02441660
Conditions: Spinal Cord Injuries Neuropathic Pain
Sponsor: The University of Texas Health Science Center at San Antonio
Start date: 2016-04-01; Completion date: 2022-05-02
Enrollment: 11 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
A prospective case control study to determine the effectiveness and longevity of 8% capsaicin patch(es) in treating neuropathic pain in persons with spinal cord injury. The investigators will study spinal cord injury patients at South Texas Veterans Health Care Systems Spinal Cord Injury inpatient unit and outpatient clinics.

Detailed description:
The investigators will recruit \~ 20 patients with chronic spinal cord injury (SCI) and chronic neuropathic pain (\>6months) below level of injury who have failed multiple pharmacological agents. Pre-study data collection will include subjective description of pain, baseline visual analog scale (VAS), numeric pain rating scale (NPRS), a numerical scale such as short form (SF) 36 form that measures quality of life parameters, subjective functional independence (FIM) scores, and pain diagrams will be obtained on each participant. Written informed consent will be obtained. After randomization patients will be assigned to a different sequence of treatment.

All patients will receive either the treatment and control patches in a randomized order for a total of three treatment periods (control, treatment, treatment for example). When assigned to received treatment arm of study patients will receive Qutenza Capsaicin 8% patch(es) applied for 1 hour after pre- treatment with topical lidocaine. The control group will receive a low dose (0.04%) amount of capsaicin in patch form using an identical application procedure.

Investigators will give each patient a diary to self record daily VAS/NPRS scores. Investigators will then schedule routine f/u via telephone call at 2, 4, 8, and 12 weeks post application to accurately report onset of relief and obtain NPRS scores at 2, 4, 8, 12 week points. Patients will follow up in clinic at the end of the 12 week study to repeat data collection using our quality of life scale (SF 36) and FIM scores. Investigators will then use data analysis to record percentage of reduction in NPRS/ VAS, and changes in SF 36 and FIM scores at any given time point vs baseline. For those that continue to have pain relief at 12 week mark we will periodically call every 4 months after study completion to assess for total duration of pain relief for up to 1 year post application.

Arms: arm 1: Qutenza, Capsaicin 8% Patch will be used for 12 weeks followed by capsacin 0.025% Well Patch arm 2: Active control with low dose capsaicin 0.025% Well Patch used for 12 weeks followed by Qutenza 8% Patch
Interventions: intervention 1: Capsaicin 8% Patch intervention 2: Low Dose Capsaicin 0.025% Well Patch
Intervention descriptions: intervention 1: Applied topically for 1 hour intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
15-322H, Trbovich, Form BC, 07-24-19, AMD.docx 
vSept3-2014 
1 
 
 
 
 
 
 
 
 
 
 
 
 
Official Study Title: Capsaicin 8% Patch for Spinal Cord Injury Neuropathic Pain 
 
 
NCT number: NCT02441660 
 
IRB Approval Date: 07.24.2019 
 
Unique Protocol ID: HSC20150322H 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Protocol Template Form 
 
Item 1 UTHSCSA 
Tracking Number 
15-322H 
 
Item 2 Abstract / 
Project Summary 
Provide a succinct and accurate description of the proposed research. State the purpose/aims. Describe 
concisely the research design and methods for achieving the stated goals. This section should be 
understandable to all members of the IRB, scientific and non-scientific.   
DO NOT EXCEED THE SPACE PROVIDED. 
Purpose/Objectives: Current pharmacologic agents for neuropathic pain (NP) in Spinal Cord Injury (SCI) provide 20-30% pain 
reduction at best; so there is clear need for research studies on new promising evidence-based therapeutic agents. Animal spinal cord 
injury models show the Transient Receptor Potential Vanilloid subfamily, member 1 (TRPV1) defunctionalization with capsaicin 
decreases nociceptor hyperactivity. Human trials are needed to substantiate this effect. Most systemic effects of oral agents often limit 
tolerability, especially as doses are titrated up to achieved maximum clinical effect. Analgesics that can be applied topically have the 
potential to largely overcome this problem; the only published study of a topical analgesic in persons with SCI examined low dose 
capsaicin cream in 8 SCI persons and found efficacy. Thus more studies on topical analgesics are needed in persons with SCI. We 
propose to conduct the first prospective trial of Capsaicin 8% (C8P)  in persons with SCI, with hopes to provide SCI patients and 
clinicians with evidence for a much-needed alternative topical therapeutic without the systemic effects that often limit tolerability.  
 
Research Design/Plan:  Randomized dual balanced 2-sequence 2-treatment, 2-period (each period is 12 weeks long), crossover 
study; with an additional prospective trial arm 
 
Methods: 
Randomized control trial: We will recruit 25 patients with chronic SCI and chronic focal neuropathic pain (>6months) below level of 
injury who have failed multiple pharmacological agents. Pre-study data collection will include subjective description of pain, baseline 
visual analog scale (VAS) and numeric pain rating scale (NPRS) values, LANNS pain score survey to accurately determine source of 
pain is neuropathic in origin,  a numerical scale such as  World Health Organization Quality of Life- (WHOQOL) brief survey 
(WHOQOL-BREF) that measures quality of life parameters, subjective SCIM (spinal cord independence measure) scores, SCI specific 
pain measures (MPI-SCI), and pain diagrams will be obtained on each participant. Written informed consent will be obtained. Each 
participant will be randomized to one of two sequences: 
Sequence 1: C8P application followed by one reapplication of a low dose capsaicin control patch (0.025% Well Patch) (available 
over the counter) 
OR 
Sequence 2: Control patch (0.025% Well Patch) followed by one replication of C8P. as indicated in Table 1.   
Measurements of the primary outcome of pain (VAS) will occur every 2 weeks and all secondary outcomes will be measured at 4,8 and 
12 weeks within each period in each sequence.  
 
Substudy: Non-randomized, non-controlled sub-study: We will also have a non-randomized non-controlled sub-study to increase data 
obtained to help calculate Number needed to treat and minimal clinically important difference for the RCT.. Patients with SCI 
undergoing patch as routine medical treatment for refractory neuropathic pain will be recruited and enrolled immediately after patch 
application. Subsequently, they will be be followed for a 12 week period using the identical protocol of sequence 1 in the RCT, without 
reapplication of a control patch.   
 
Clinical Relevance:  Potentially giving analgesic pain relief for spinal cord focal peripheral neuropathic pain without the hand strength 
or dexterity required to open bottles, take oral tablets/capsules, or apply a transdermal patch, cream or ointment on a daily basis. 
 
Item 3 
Background 
 
Describe past experimental 
and/or clinical findings 
leading to the formulation 
of your study.   
For research involving 
unapproved drugs, describe 
animal and human studies.   
For research that involves 
approved drugs or devices, 
describe the FDA approved 
uses of this drug/device in 
Capsaicin 8% patch (Qutenza) is an FDA approved treatment for neuropathic pain in post herpetic 
neuralgia (PHN). After the FDA approval of Qutenza several studies have been published assessing the 
efficacy and safety in patients with HIV autonomic neuropathy and PHN. In a meta-analysis examining 
2057 persons with PHN and HIV-AN, the proportion of responders with relief (>30% improvement in pain 
lasting from 2-12 weeks) over a 12-week treatment period was 43% in the C8P group and 34% in the 
control group, a statistically significant difference.   
A retrospective review  by Dr. Trbovich and Dr. Huiqing Yang pending publication in the American 
Journal of Physical Medicine and Rehabilitation also supports that Capsaicin 8% patch provided all three 
patients in the study had complete relief of pain on average after 2 weeks for an average duration of 169 
days. 


15-322H, Trbovich, Form BC, 07-24-19, AMD.docx 
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3 
relation to your protocol. 
Item 4 
Purpose and rationale 
Insert purpose, objectives 
and research 
questions/hypotheses here. 
 If you cut and paste from 
another document, make 
sure the excerpted material 
answers the question 
While low dose capsaicin cream has shown efficacy with minimal side effects in radicular pain of 8 SCI 
persons, short dosing intervals (every 1-4 hours) and poor manual dexterity of persons with SCI (e.g., 
tetraplegia) can impair efficacy and adherence. Thus the novelty of high dose capsaicin is that a single 
topical application of the C8P for only 1 hour could potentially provide pain relief for 8-12 weeks. 
 
 
 
Item 5 
Study Population(s) Being Recruited 
 
In your recruitment plan, how many 
different populations of prospective 
subjects do you plan to target? 
Provide number: 2 
 
 
 
Identify the criteria for inclusion: 
 
 
 
Identify the criteria for exclusion: 
4.  
e.g., a population can be individuals 
with type 2 diabetes controlled with diet 
and/or a population of healthy controls.  
Or a population can be individuals 
attending an education program, etc. 
 
List each different population on a 
separate row and provide a short 
descriptive label:   
(e.g., normal-healthy, diabetics, 
parents, children, etc.) 
 
To add rows use copy & paste 
 
Spinal cord injury patients with 
neuropathic pain for RCT 
1. Diagnosis of SCI 
2. Neuropathic pain below level of injury 
3. Surface area of pain no larger than 2 
patches 
4. Failed or did not tolerate gabapentin 
3600mg/day, pregabalin 600mg/day, 
capsaicin cream and/or lidocaine cream 
5. Skin over painful area intact 
 
1. Pain over open wound 
2. Previously documented allergy to capsaicin 
3. Superficial burn over area of pain 
5. Premorbid (before SCI) neuropathic pain 
6.  HIV/AIDS neuropathy 
7. Uncontrolled hypertension or autonomic 
dysreflexia 
8. 
Previous application of capsaicin 
patch 
Spinal cord injury patients with 
neuropathic pain for prospective trial 
arm 
1. Diagnosis of SCI 
2. Neuropathic pain  
4. Failed or did not tolerate gabapentin 
3600mg/day, pregabalin 600mg/day, 
capsaicin cream and/or lidocaine cream 
5. Skin over painful area intact 
6. have been prescribed the C8P as routine 
clinical care treatment 
1. Pain over open wound 
2. Previously documented allergy to capsaicin 
3. Superficial burn over area of pain 
9. Premorbid (before SCI) neuropathic pain 
10. 
6. HIV/AIDS neuropathy 
11. 
Uncontrolled hypertension or 
autonomic dysreflexia 
 
 
 


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4 
Item 6 
Research Plan / Description of the Research Methods a.  Provide a comprehensive narrative describing the research methods.   
Provide the plan for data analysis (include as applicable the sample size calculation). 
 
Step-by-Step Methods:  
 
RECRUITMENT: 
RCT: We will identify 25 patients with chronic SCI from our VA SCI clinic, UH SCI and Rehabilitation Clinics, and/or local SCI 
population. We will recruit with flyers at the VA and UHS. We will utilize chart review and patient interview to ensure 
patients) meet inclusion criteria above and have failed multiple pharmacological agents. We will gather demographics, 
clinical history, and imaging on each patient via chart review.  SCI attending Dr. Michelle Trbovich or one of the four 
residents participating in this research- Esha Lukose, Wesley Peace, Brett Helmonds, or Colby Beal- will contact patients 
that are appropriate study subjects regarding recruitment for the study and to invite patients to come an outpatient SCI 
clinic to consent to participate in this prospective study. Each patient’s pain will be classified based on a taxonomy utilized 
by the validated and reliable International Spinal Cord Injury Pain Basic Data Set (ISCIPDS). The ISCIPDS classifies NP into 
three groups: “at level”, “below level”, and “other.” 24 “At level” and “below level” pain must be directly related to SCI 
(central nerve injury) and are the only subjects that will be included in this study. Pain will also be validated with the 
LANNS pain score survey, which is an accurate tool for validation of pain which is neuropathic in origin.  
 
Substudy: Non- randomized, non-controlled arm: The VA SCI clinic routinely applies the C8P to patients as an off-label 
treatment for refractory pain control. When a patient has been identified to have had the patch placed, we will consent, 
enroll him/her and follow him every 2 weeks to collect primary and every 4 weeks to collect secondary outcome data as 
described in the RCT. We aim to enroll 50 persons in this arm of the trial. 
 
CONSENT: 
RCT and substudy: 
Patients will be approached in a private outpatient room in the spinal cord injury clinic or inpatient room.or via telephone. 
Risks, benefits, alternative options will be shared and the subjects will be allowed to ask any questions they may have to 
ensure they understand the risks, benefits and goal of study.    
 
PRE STUDY DATA COLLECTION: 
 RCT: Pre-study data including subjective description of pain, baseline VAS, LANNS and NPRS . Pre-study data collection will 
include an intake form with subjective description of pain, baseline VAS / LANNS/NPRS, a numerical scale such as SF36 
that measures quality of life parameters, subjective FIM scores, and pain diagrams will be obtained on each participant via 
the outpatient spinal cord injury clinic, or inpatient spinal cord injury unit.  
 
Substudy: Non randomized, non-controlled arm: no pre-study data collection. 
RANDOMIZATION: (RCT only) 
Randomized dual balanced 2-sequence 2-treatment, 3-period, crossover study (see Table 1). 
Tale 1.  The proposed study layout 
 
 
Period 
Sequence 
1 
2 
1 
2 
A 
B 
B 
A 
 
Where A indicates 8% Capsaicin and B indicates Low dose capsaicin control patch [1]. Each treatment period will be 12 
weeks in duration.  The proposed design is a standard 2-period, 2-treatment, 2-sequence design. 
Inclusion criteria: >1year post SCI, chronic neuropathic pain with VAS>3, pain below the level of injury and failure of at least 
3 oral or topical pharmacological agents.  Exclusion criteria: painful area >1120cm2 (4 patches), skin breakdown over area 
and uncontrolled hypertension.   
 
Methods: 
RCT: Each participant will be randomized to one of two sequences: 
Sequence 1: C8P application followed by one reapplication of a low dose capsaicin control patch (0.025% Well Patch) 
(available over the counter) 
OR 
Sequence 2: Control patch (0.025% Well Patch) followed by one replication of C8P, as indicated in Table 1.   
 
Patch application method: Per manufacturers’ application directions, the painful area will be treated with topical lidocaine 


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5 
2.5%/prilocaine 2.5% for 1 hour prior to application of the test patch(es). Active and control patches will then be applied and 
left in place for one hour.  After removal, the cooling gel will be applied to decrease any burning sensation from the capsaicin, 
per manufacturers’ protocol.  Blood pressure will be monitored every 30minutes after the capsaicin (control or treatment) 
patch over the hour of application. 
 
Substudy: Non-randomized, non-controlled prospective arm: Patients with SCI undergoing patch as routine medical 
treatment for refractory neuropathic pain will be recruited and enrolled immediately after patch application. Subsequently, 
they will be followed for a 12 week period using the identical protocol of data collection post patch application in the RCT, 
without reapplication of a control patch.   
 
 
Post patch application data collection  (RCT and substudy): Measurements of the primary outcome (VAS) will occur every 2 
weeks and all secondary outcomes will be measured at 4, 8 and 12 weeks within each period in each sequence.  Every 2 
week VAS scores will be collected via phone at weeks 2,6,10 and in person at weeks 4, 8, 12. All secondary outcomes 
surveys will be done at a face to face visit at weeks 4, 8, 12. 
 
 
 
Outcome measures:  (RCT and substudy) 
: Primary efficacy endpoint is the visual analog scale (VAS) score at the end of each of the three 12-week periods (at weeks 
12 and 24). Secondary outcome measures include the Multidimensional Pain Inventory (MPI) Pain Severity Subscale, MPI-
SCI, International SCI Pain Basic Data Subset (SCIPBDS), WHOQOL-BREF, Spinal Cord Independence Measure (SCIM) 
and number of concomitant pain medications 
 
Specific Aims:  
1. Determine the effect of the capsaicin 8% patch on VAS scores.  
2. Determine the effect of the 8% Capsaicin (C8P) on QOL.  
3. Determine the effect of the C8P on physical function. . 
 
 
UHS clinic sites: Patients will be approached by providers (who are also investigators in this study), regarding being 
contacted by phone to hear more about the study. If agreeable patient’s name and phone number will be provided 
manually/verbally to the study team at the VA in order to contact interested patients. No PHI will be transferred 
electronically between UHS and the VA. Data for the study will be provided by patient and collected at the VA.  
 
Data Analysis Plan:  
RCT: Due to the small population of individuals with a spinal cord injury and high incidence of neuropathic pain in such 
persons and lack of prospective studies on the capsaicin 8% patch, we felt a small group of 25 patients was large enough 
to show possible potential benefits, small enough to realistically complete this study, follow patients appropriately 
according to standard of care, and in congruence with the small population size commonly seen in spinal cord injury 
studies.  This study will serve as pilot data for a larger study in the future. 
Substudy: Non-randomized, non-controlled arm: 50 participants will be enrolled and we will use the baseline and post 
patch application data to help determine the number needed to treat and minimal clinically important difference for the 
RCT. 
 
RCT and substudy: Data analysis will be performed on subjective description of pain at baseline from NPRS, VAS and 
evaluated at 2, 4, 8, 12 weeks post application to determine efficacy of capsaicin 8% patch in regards to point value and 
percentage of reduction compared to baseline. Longevity as recorded by reduction in baseline NPRS and VAS scores in 
days, weeks, and months of relief until pain returns to baseline. We will also compare our quality of life scale (WHO-QOL) 
and SCIM scores from pre study to post study and evaluate for more subjective measures of improvement in quality of life 
and functional improvement respectively.  In the RCT trial we will assess for significant differences is outcomes between 
the treatment and control groups over time whereas, in the non-randomized, non-controlled trial we will compare 
baseline scores to 12 weeks post patch application scores for all outcomes. The significance of variation in the mean 
outcome with treatment will be assessed with a mixed effects linear model of the outcome in terms of sequence, subject 
nested in sequence, period, treatment, and first order carryover.  All statistical testing will be two-sided with a significance 
level of 5%.  SAS Version 9.4 for Windows or later, SAS Instititue, Cary, North Carolina, or R will be used throughout.   
 
 
 


15-322H, Trbovich, Form BC, 07-24-19, AMD.docx                                    vSept3-2014                                                                                                                                                                                                                                        6 
 
 
Item 7 Risks Section: 
Complete the following table to describe the risks of all research procedures listed in Step 2, Institutional Form (items 28-34).  Do not list risks of Routine care 
procedures here.  
 ☒ N/A, Risks are described in the informed consent document – do not complete this table. 
Research procedures 
 
example: 
• 
History and physical 
• 
Questionnaire 
• 
Laboratory tests 
 
Add or delete rows as needed 
Risks 
 
List the reasonably expected risks 
under the following categories as appropriate: 
 
o  
 
o  
 
o