Clinical trial NCT03770091
Conditions: Arthritis
Sponsor: John Fowler
Start date: 2018-12-21; Completion date: 2020-08-01
Enrollment: 40 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Thumb carpometacarpal osteoarthritis (CMC OA) affects up to 33% of people over the age of 40, which leads to inflammation, pain, and weakness of the CMC joint. Treatment modalities are both conservative and surgical with surgical options including osteotomy, bone excision, ligament reconstruction, and various prosthetic implants. The conservative treatment options, however, are limited to NSAIDs and bracing or steroid injections.

Advances in topical therapies have the potential to deliver focused treatment to the CMC joint. Novel treatment of inflammation can potentially reduce inflammation and pain associated with progressing osteoarthritis. Theraworx Relief is an FDA registered foam that has theoretical impact on inflammation reduction in human subjects treated with the topical foam.

Detailed description:
This pilot study seeks to investigate potential benefit in the use of Theraworx Foam in patients diagnosed with thumb CMC OA. Patients presenting to the upper extremity orthopedic surgery clinic for thumb/hand/wrist pain will be diagnosed by a Board Certified Hand Surgeon as per standard protocols. Patients who are recommended to follow a conservative treatment modality and are interested in participating in this study will be randomized into treatment or control groups. Both groups will undergo symptom assessment, strength testing, and range of motion testing prior to starting the standard conservative treatment of bracing. The treatment group will use the TheraWorx topical foam and the compression wrap nightly for 2 weeks for at least 6 hours per night. Control group will use a compression wrap for the same time period. Both groups will return at 1 and 2 weeks for repeat strength and range of motion testing and symptom assessment.

Arms: arm 1: Patients will use Theraworx foam and a compression wrap arm 2: Patients will use placebo foam and a compression wrap arm 3: Patients will use Theraworx foam without compression wrap
Interventions: intervention 1: Theraworx intervention 2: Placebo
Intervention descriptions: intervention 1: Theraworx foam applied to skin and/or compression wrap intervention 2: Placebo foam

Protocol documents:
Prot_SAP_001.pdf: 
Date: Thursday, April 4, 2019 9:59:30 AM
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View: Pitt SF: Basic Information
Basic Information
Basic Information
1. * * Title of study:
Impact of Theraworx Foam on Pain and Motion and Patient-Reported Outcomes in
Thumb Arthritis
2. * * Short title:
Theraworx Foam
3. * * Brief description:
Thumb carpometacarpal osteoarthritis (CMC OA) affects up to 33% of people over
the age of 40, which leads to inflammation, pain, and weakness of the CMC joint.
Treatment modalities are both conservative and surgical with surgical options
including osteotomy,
bone excision, ligament reconstruction, and various prosthetic implants. The
conservative treatment options, however, are limited to NSAIDs and bracing or
steroid injections.
Advances in topical therapies have the potential to deliver focused treatment to the
CMC joint. Novel treatment of inflammation can potentially reduce inflammation and
pain associated with progressing osteoarthritis. Theraworx Relief is an FDA
registered foam that has theoretical impact on inflammation reduction in human
subjects treated with the topical foam. 
This pilot study seeks to investigate potential benefit in the use of Theraworx Foam
in patients diagnosed with thumb CMC OA. Patients presenting to our upper
extremity orthopedic surgery clinic for thumb/hand/wrist pain will be diagnosed by a
Board Certified Hand
Surgeon as per standard protocols. Patients who are recommended to follow a
conservative treatment modality and are interested in participating in this study will
be randomized into treatment or control groups. Both groups will undergo symptom
assessment, strength testing, and range of motion testing prior to starting the
NCT03770091
Official Title: Impact of Theraworx Foam on Pain and Motion and Patient-
Reported Outcomes in Thumb Arthritis
Document Date: August 1, 2020


standard
conservative treatment of bracing. The treatment group will use the TheraWorx
topical foam and the compression wrap nightly for 2 weeks for at least 6 hours per
night. Control group will use a compression wrap for the same time period. Both
groups will return at 1 and 2 weeks for repeat strength and range of motion testing
and symptom assessment.
4. * * Principal investigator:
John Fowler
5. * * Does the investigator have a financial interest related to this research?
○␣
○␣Yes ○No
6. * * Will an external IRB act as the IRB of record for this study?
○␣
○␣Yes ○No
7. * * What kind of study is this?
Single-site study
8. Attach the protocol:
Sponsor/Multicenter protocol
Investigator-initiated protocol
Emergency Use Consent/ Protocol/ FDA Form 3926
Exempt Application form
Document
Category
Date Modified
Document History
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View: Pitt SF: Study Aims
Study Aims
Study Aims
1. * * Describe the purpose, specific aims, or objectives and state the hypotheses
to be tested:
The purpose of this study is to assess the efficacy of Theraworx foam in reduction of
inflammation and pain as measured by subjective pain/disability scales, motion, and
strength testing.
Specific Aim 1: To assess the efficacy of Theraworx foam in reduction of pain on
subjective pain/disability scales for thumb CMC arthritis.
- Hypothesis 1a: Patients given the Theraworx foam and compression wrap will see
significant improvements in reported Numeric Pain Rating Scale (NPRS) compared
to patients who are given the placebo foam and compression wrap and Theraworx
foam alone.
- Hypothesis 1b: Patients given the Theraworx foam and compression wrap will see
significant improvements in score on the Disabilities of the Arm, Shoulder, and Hand
(DASH) questionnaire compared to patients who are given the placebo foam and
compression wrap and Theraworx foam alone.
Specific Aim 2: To assess the efficacy of Theraworx foam to improve function and
patient reported outcomes for thumb CMC arthritis.
- Hypothesis 2a: Patients given the Theraworx foam and compression wrap will see
significant improvements wrist range of motion compared to patients who are given
the placebo foam and compression wrap and Theraworx foam alone.
-Hypothesis 2b: Patients given the Theraworx foam and compression wrap will see
significant improvements in grip and pinch strength compared to patients who are
given the placebo foam and compression wrap and Theraworx foam alone.
2. * * Describe the relevant prior experience and gaps in current knowledge
including preliminary data. Provide for the scientific or scholarly background
for, rationale for, and significance of the research based on existing literature
and how it will add to existing knowledge:
Recent research surrounding the structure and function of the outermost layers of


skin have provided insights into potential avenues for improved health. The skin,
primarily the stratum corneum was conventionally described as a biologically inert
layer, comprised of keratin and dead epidermal cells. The scientific understanding of
the stratum corneum has evolved to see a more dynamic and critical structure to
skin health. This barrier has a major
role in inflammatory regulation of underlying skin, barrier protection from infection
and maintenance of superficial pH that modulates bacterial flora growth and sweat
loss.(5,6) Stratum corneum health allows for a multitude of protective functions. The
stratum corneum maintains skin pH at approximately 5.0, which allows for healthy
flora to exist and
deters pathogenic flora colonization. Exogenous rise in skin pH or psychological
stress, impacts the skin function, including inflammatory cascade modulation.(7)
This is where investigation of agents that maintain stratum corneum integrity can
impact the health and physiologic functions of the skin in patients with inflammatory
disease.
The need for improved conservative treatment approaches to thumb CMC OA is
increasing with increased population longevity and increased rates of OA in younger
populations.(8) The Theraworx topical agent is an FDA-registered product and
received approval for commercial labelling. The use of plant extracts in Thearworx,
such as Aloe Vera, makes it a potent moisturizing agent, but the extracts in
Theraworx also have antiinflammatory
and pain reducing effects. Allantoin, which has been used in cosmetic
preparations for many years, moisturizes by increasing the water content and
enhancing health of the upper layers of dead skin cells, helping improve wound
healing and injuries of the skin. Beta-Glucan 1,3D is a complex carbohydrate that
has been demonstrated to enhance the effectiveness of inflammatory responses
within the skin and subcutaneous
tissue. These components have potential to impact acute inflammatory responses
and promote more rapid healing than non-treatment. (5,6)
Previously completed studies on Theraworx foam have shown no allergic reaction at
all in all patients as well as being a non-irritant for all patients. (9)
Significance: If the Theraworx foam and/or Theraworx foam with compression wrap
can be shown to reduce pain and allow for improved functional measures, the
product can be proposed as an option for conservative treatment of thumb CMC OA
and reduce the reliance on oral pain medications, steroid injections, and surgery.


View: Pitt SF: Study Design
Study Design
Study Design
1. Total number of subjects to be enrolled at this site (enter -1 for chart reviews,
banking, registries):
60
2. Describe and explain the study design:
After informed consent, subjects will be randomized to one of three groups:
1. Theraworx foam with compression wrap
2. Placebo foam with compression wrap
3. Theraworx foam alone
Baseline testing will include Numeric Pain Rating Scale (NPRS). The Disabilities of
the Arm, Shoulder, and Hand (DASH) will be administered to the participant by the
study coordinator. Static range of motion will be tested with a wrist goniometer
measuring flexion, extension, ulnar deviation, and radial deviation with the
participant's elbow supported on a hand table. Strength testing will be performed
with a hand dynamometer and pinch meter. These questionnaires/tests will be
performed at baseline, 1 week, and 2 week visits. They should take approximately
10 minutes to complete.
Subjects will be instructed to apply the foam every night (two pumps and rub into the
base of the thumb). This will be demonstrated by the research coordinator (to be
hired and added to this IRB application). 
Participants will be asked to apply the foam nightly for a minimum of 6 and
maximum 10 of hours and avoid use of lotions, topical creams, or topical NSAIDs
during the study period. Subjects will be advised to avoid other oral prescription or
OTC pain relief medications during the 2-week study period. A study data sheet will
be given at this time for the participant to document nightly compliance hours, daily
Tylenol use, and daily pain rating. This sheet will be collected at the 2 week visit.
This portion of the research visit should take approximately 5 minutes but will allow
for time for questions.
Randomization will occur via block randomization designed to randomize subjects
into groups that result in equal sample sizes.


3. Describe the primary and secondary study endpoints:
All endpoints are primary:
1. Numeric Pain Rating Scale
2. Disabilities of the Arm, Shoulder, and Hand (DASH)
3. Pinch strength
4. Grip strength
5. Thumb range of motion
4. Provide a description of the following study timelines:
Duration of an individual subject's active participation:
2 weeks
Duration anticipated to enroll all subjects:
1 year
Estimated date for the investigator to complete this study (complete primary
analyses): 
9/30/2019
5. List the inclusion criteria:
Patients of John Fowler, the PI, with the following:
1. Thumb CMC arthritis
2. greater than or equal to age 18
3. Interested in non-operative treatment of thumb arthritis
6. List the exclusion criteria:
1. Recent corticosteroid injection into the thumb joint
2. Non-English speaking
3. skin lesions or rashes on the thumb
4. current use of topical anti-inflammatory medications
5. concomitant thumb/wrist diagnoses that would impact the results (as determined
by the PI)
6. known allergy to magnesium
7. Will children or any gender, racial or ethnic subgroups be explicitly excluded
from participation?
○Yes ○␣
○␣No
* Identify the subgroups and provide a justification:


Children - arthritis of the thumb CMC joint does not typically exist in subjects less
than the age of 18 and including a rare patient that might have CMC arthritis would
bias our results.
8. Describe the power analysis used and cite your method of statistical analysis.
If a power analysis is not possible, thoroughly justify the sample size required
for the study, including appropriate literature citation (alternatively provide
page reference in attached protocol):
The mean pain reported in subjects with CMC arthritis is 5 (out of 10) on the
numeric pain rating scale. Assuming a clinical meaningful change in pain of 2 on this
scale, an alpha of 0.05 and beta of 0.2, the power analysis demonstrates 16
subjects required per group. Assuming a drop out rate of 20%, we will enroll 20
subjects per group.


View: Pitt SF: Research Activities
Research Activities
Research Activities
1. * * Provide a detailed description of all research activities (including screening
and follow-up procedures) that will be performed for the purpose of this
research study. This description of activities should be complete and of
sufficient detail to permit an assessment of associated risks.
Screening and Enrollment: Patients diagnosed with thumb CMC OA by the PI and
recommended for participation in the study will be assessed for inclusion and
exclusion criteria appropriateness by the study coordinator. If they are candidates,
consent will be obtained by the PI in a private room and they will be randomized into
treatment or control group by the coordinator. At this time, the x-ray taken during
routine care by the PI for diagnosis will be obtained and graded for severity.
Demographic information including age and gender will also be collected.
Research Visits: Baseline, 1 week and 2 week visits
Study procedures will be performed by the study coordinator in a patient room
equipped with a hand table, if necessary, patient will be moved to an procedure
room similarly equipped. Numeric Pain Rating Scale (NPRS), and Disabilities of the
Arm, Shoulder, and Hand (DASH) will be administered to the participant by the study
coordinator. Static range of motion will be tested with a wrist goniometer measuring
flexion, extension, ulnar deviation, and radial deviation with the participant's elbow
supported on a hand table. Strength testing will be performed with a hand
dynamometer and pinch meter. These questionnaires/tests will be performed at the
baseline, 1 week and 2 week visits. They should take approximately 10 minutes to
complete. Study coordinator will also provide the participant with the foam and
compression wraps and provide instructions for its use. The compression wrap is a
cloth wrap (similar to an elastic bandage wrap) that will be saturated/treated with the
Theraworx foam. Participants will be asked to apply the foam treated wrap nightly
for a minimum of 6 and maximum 10 of hours and avoid use of lotions, topical
creams, or topical NSAIDs during the study period. A study data sheet will be given
at this time for the participant to document nightly compliance hours, daily Tylenol
use, and daily pain rating. This sheet will be collected at the 2 week visit. This
portion of the research visit should take approximately 5 minutes but will allow for
time for questions.
2. Upload a copy of all materials used to collect data about subjects: (Attach all
surveys, interview/focus group scripts, and data collection forms except for
case report forms, SCID or KSADS):


Document
Category Date
Modified
Document
History
View Foam%20Study%20Data%20Form.pdf(0.02)
Data
Collection10/9/2018History
View DASH_questionnaire_2010.pdf(0.02)
Data
Collection10/9/2018History
View Numeric%20Pain%20Rating%20Scale%20Instructions.pdf(0.01)Data
Collection9/30/2018History
3. * * Will blood samples be obtained for research purposes?
○␣
○␣Yes ○No
Unique Protocol ID: STUDY18090019
Official Title: Impact of Theraworx Foam on Pain and Motion and Patient-
Reported Outcomes in Thumb Arthritis
Document Date: August 1, 2020


View: Pitt SF: Data Safety and Monitoring
Data Safety and Monitoring
Data Safety and Monitoring
1. * * Describe your plan to periodically evaluate the data collected regarding
both harms and benefits to determine whether subjects remain safe.  The plan
might include establishing a data monitoring committee and a plan for
reporting data monitoring committee findings to the IRB and the sponsor:
The primary investigator will monitor confidentiality and data on a monthly basis to
ensure accuracy and recruitment of subjects. Monthly meetings, with the study
coordinator will be held to verify compliance and testing procedures. These
meetings will monitor recruitment, retention, data, adverse events, and breaches in
confidentiality.
The investigators will comply with the IRB’s policies for the reporting of serious and
unexpected adverse events as addressed in Chapter XVII of the IRB Policies and
Procedures Manual.
At the time of the IRB renewal, the PI will submit in writing the information about the
frequency of the monitoring, the dates that the weekly meetings took place, a
summary of the cumulative adverse events, external factors or relevant information
that might have an impact on the safety or ethics of the study, and final conclusion
regarding changes to the anticipated risk/benefit ratio to study participation and final
recommendations related to the
continuation, changing, or termination of the study. Also, at the time of the IRB
annual renewal, reported documentation over the past year will be submitted to the
IRB.
2.
* * Describe your plan for sharing data and/or specimens:
Though we currently do not have plans to share data/documents to external
persons, if at a future time we wish to share information appropriate approvals will
be obtained.
3. If any research data is collected, stored, or shared in a paper format, address
what precautions will be used to maintain the confidentiality of the data:
Paper-based records will be kept in a locked filing cabinet and only be accessible to
personnel involved in the study. Computer-based files will only be made available to
personnel involved in the study through the use of access privileges and passwords
and stored on an encrypted /firewall protected network.


View: Pitt SF: Risk and Benefits
Risk and Beneﬁts
Risk and Beneﬁts
1. * *  Enter all reasonably foreseeable risks, discomforts, hazards, or
inconveniences to the subjects related to subjects’ participation in the
research:
View
Research Activity
Strength Testing 
Common Risks
No Value Entered 
Infrequent Risks
Isometric strength testing may result in muscle cramping, discomfort, or
fatigue, although occurrence is rare (occurs in less than 1% of people). 
Other Risks
No Value Entered 
View
Research Activity
Randomization 
Common Risks
Those being randomized to the placebo may not receive direct benefit
compared to those randomized to foam. 
Infrequent Risks
No Value Entered 
Other Risks
No Value Entered 
View
Research Activity
Use of Foam 
Common Risks
No Value Entered 
Infrequent Risks
Skin irritation, allergic reaction 
Other Risks
No Value Entered 
View
Research Activity
Storage of Research Data 
Common Risks
No Value Entered 
Infrequent Risks
Breach of Confidentiality 
Other Risks
No Value Entered 
View
Research Activity
Range of Motion Testing 
Common Risks
No Value Entered 
Infrequent Risks
The range of motion procedures may result in soreness, however it is rare
(occurs in less than 1% of people). 


Other Risks
No Value Entered 
2. * *  Describe the steps that will be taken to prevent or to minimize risks:
Subject research records will be double-locked, with access only be research
personnel listed. Electronic files will be stored in password protected systems.
Subject research records and the data linking file will be destroyed after 7 years to
decrease the risk of confidentiality being breached.
Subjects will be instructed to not exert themselves in a manner that will cause pain
during the procedures. Those who experience any pain or discomfort during the
testing procedures will be given the opportunity to rest or terminate the testing
session.
Subjects with any prior adverse reactions to topical agents will be excluded.
In the event of any adverse event or injury, the investigator will provide the subject
for proper medical treatment.
3. Financial risks - will the subject or insurer be charged for any research
required procedures?
○␣
○␣Yes ○No
4. Describe the steps that will be taken to protect subjects’ privacy:
Examination and testing will be completed in a private examination room
5. What steps will be taken in the event that a clinically significant, unexpected
disease or condition is identified during the conduct of the study:
The PI will notify the patient and either treat the condition or provide an appropriate
referral.
6. Describe the potential benefit that individual subjects may experience from
taking part in the research or indicate if there is no direct benefit. Do not
include benefits to society or others:
There may be a direct benefit for participating in this study, if the study hypothesis is
true, there is a chance that the treated wrap will provide more pain relief and
inflammation reduction than the placebo wrap/bracing alone.
The data gathered will allow us to determine if there is a benefit to the test foam in
reducing pain and inflammation in thumb


CMC OA. Having an understanding of the product in recovery may lead to future
studies that investigate a wider array of measures related to conservative CMC OA
treatment.
7. Do you anticipate any circumstances under which subjects might be
withdrawn from the research without their consent?
○Yes ○␣
○␣No
* Describe the circumstances and any procedures for orderly termination:
unforeseen illness or allergic reaction to foam or non-compliance
8. Describe procedures that will be followed when subjects withdraw from the
research, including partial withdrawal from procedures with continued data
collection and data already collected:
The data already collected will continue to be used in the study.


View: Pitt SF: Placebo Arm
Placebo Arm
Placebo Arm
1. * *  Is there a commonly used diagnostic/treatment approach that is currently
recognized as being effective for the proposed subjects' disease or condition,
and that will be withheld from subjects assigned to the placebo arm of this
research study:
Yes
2. Describe the commonly used diagnostic/treatment approaches that will be
withheld from subjects assigned to the placebo arm of this research study:
A commonly used treatment approach is corticosteroid injection, over the counter
pain medications, and/or surgical treatment.
3. Is enrollment into this study limited to individuals in whom the commonly
used diagnostic/treatment approaches are known to be ineffective or
intolerable?
no
4. Provide a scientific justification for the placebo-control arm of this research
study:
The study purpose is to compare the use of TheraWorx foam and compression
wrap, with the placebo foam with wrap and Theraworx foam alone on subjects with
thumb carpometacarpal osteoarthritis having thumb or wrist pain.
5. How long will subjects participate in the placebo arm?  Justify why this
duration is necessary:
2 weeks. This is a short period of time. If no benefit in the placebo arm, can
efficiently undergo other treatment options such as steroid injection.
6. How frequently will the subject's condition or disease be monitored and
compare that to the frequency of monitoring associated with standard care for
this disease/condition?
weekly
7. What specific endpoints will result in discontinuing a subject's participation
due to worsening of the subject's disease or condition?
It is such a short study and examining a chronic condition (arthritis) that the PI does


not expect an acute worsening of the disease or condition.
8. What is the risk to subjects who receive no active treatment for their disease
or condition while in the placebo arm?
Felay in treatment by usual care conservative measures resulting in pain
9. Describe the planned involvement of a 'contact person' who interacts with the
subject on a regular basis and who will notify the investigators immediately of
any problems related to the subject's disease or condition:
There is no reason why the subject could not contact the investigators in this study
on thumb arthritis. No plans to involve a contact person.
Note: The involvement of the contact person must also be addressed in the consent
form


View: Pitt Create
Statistical Analysis Plan
The Primary Outcome is VAS pain score at 2 weeks
This will be analyzed with ANOVA which is the appropriate test for 
continuous data and multiple groups.
Significance will be set at 0.05
Secondary Outcomes
Will also be analyzed using ANOVA.
Significance will be set at 0.05