Effects of Subcutaneous Hyaluronidase Administration on Psoriatic Plaques
| Status: | Completed |
|---|---|
| Conditions: | Psoriasis |
| Therapuetic Areas: | Dermatology / Plastic Surgery |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 1/6/2019 |
| Start Date: | July 2015 |
| End Date: | February 2018 |
Evaluation of the Effect of Subcutaneous Hyaluronidase Administration on Psoriatic Plaques
Dendritic cells are a key component of the inflammatory response seen in psoriasis. Several
current psoriasis therapies have been shown to reduce the number of dendritic cells in
patients with psoriasis, leading researchers to believe that therapies specifically targeting
dendritic cells may lead to improvement in psoriasis. Research recently conducted in Dr.
Gallo's lab at the University of California San Diego has shown that transgenic mice
overexpressing the enzyme hyaluronidase have a significant decrease in the number of
dendritic cells in the dermal component of their skin compared to wild type mice. If
hyaluronidase overexpression in humans also decreases the number of dendritic cells in the
dermis, then hyaluronidase therapy may improve the clinical presentation of psoriasis. In
order to test this hypothesis, recombinant human hyaluronidase (Hylenex®) will be injected
subcutaneously below a psoriatic plaque in human psoriasis patients every week for a total of
4 weeks. Each week the clinical appearance of the plaque will be documented. At the final
visit skin biopsies of the treated plaque will be taken to visualize the histology of the
plaque and look for changes in expression of different inflammatory markers.
current psoriasis therapies have been shown to reduce the number of dendritic cells in
patients with psoriasis, leading researchers to believe that therapies specifically targeting
dendritic cells may lead to improvement in psoriasis. Research recently conducted in Dr.
Gallo's lab at the University of California San Diego has shown that transgenic mice
overexpressing the enzyme hyaluronidase have a significant decrease in the number of
dendritic cells in the dermal component of their skin compared to wild type mice. If
hyaluronidase overexpression in humans also decreases the number of dendritic cells in the
dermis, then hyaluronidase therapy may improve the clinical presentation of psoriasis. In
order to test this hypothesis, recombinant human hyaluronidase (Hylenex®) will be injected
subcutaneously below a psoriatic plaque in human psoriasis patients every week for a total of
4 weeks. Each week the clinical appearance of the plaque will be documented. At the final
visit skin biopsies of the treated plaque will be taken to visualize the histology of the
plaque and look for changes in expression of different inflammatory markers.
Participation in this study will consist of a total of 5 visits to the UCSD Dermatology
Clinic over approximately a one-month period. At the first visit, two psoriatic plaques
between 2-cm and 5-cm in diameter to be studied in this trial will be agreed upon by the
patient as well as the blinded and unblinded investigators. Preference will be given to
plaques on the elbows since the elbow is a common place of psoriatic plaques, and since
scarring on the elbows is usually more acceptable than scarring on other parts of the skin
since the skin on the elbows is naturally hyperpigmented in most people. For the remainder of
the study, all grading and measurements of the psoriatic plaques will be completed by a
blinded investigator who is unaware of which plaque is receiving which treatment. An
unblinded investigator will complete all other portions of the study visit, including digital
photography, injecting the plaques, and completing the biopsies. The subject will also be
blinded as to which plaque is being injected with which treatment.
During the first 4 visits, plaques will be injected with 1-mL of Hylenex® or 1-mL of sterile
(pharmaceutical grade) normal saline (NS). 1-mL of Hylenex® contains 150 Units of recombinant
hyaluronidase. This is the standard dose of the drug that has been approved by the FDA, and
therefore this dose is considered to be safe for use in adults. If injected subcutaneously
into the center of a psoriatic plaque that is between 2 and 5 centimeters in diameter, this
1-mL dose should be able to diffuse throughout the entire area beneath the plaque. The exact
pharmacokinetics of Hylenex® are difficult to study due to its rapid inactivation after
intravenous injection. According to the Hylenex® package insert, though, disruptions to the
dermal barrier that occur in response to subcutaneous Hylenex® injection persist 24 hours
after injection, but this barrier is completely restored after 48 hours. Cutaneous dendritic
cells residing in the epidermis are thought to migrate away from the epidermis through either
lymphatic or vascular channels after Hylenex® is injected. This process should take a few
hours. Since cutaneous dendritic cells are thought to turnover only every several weeks, new
dendritic cells should not populate the epidermis before patients receive the next injection
of Hylenex®. Since dendritic cell activation initiates the inflammatory cascade thought to
result in psoriasis, preventing dendritic cells from being harbored in the epidermis should
essentially prevent the inflammatory cascade that results in psoriasis. Therefore, during the
month-long period while patients are receiving Hylenex® injections, the inflammatory cascade
triggering their psoriasis will potentially be turned off, allowing affected plaques to heal
without propagation of further psoriasis. If this is true, there should be differences in the
Hylenex®-treated versus the NS-treated plaques both morphologically and histologically upon
completion of the final set of biopsies on the Visit 5.
Clinic over approximately a one-month period. At the first visit, two psoriatic plaques
between 2-cm and 5-cm in diameter to be studied in this trial will be agreed upon by the
patient as well as the blinded and unblinded investigators. Preference will be given to
plaques on the elbows since the elbow is a common place of psoriatic plaques, and since
scarring on the elbows is usually more acceptable than scarring on other parts of the skin
since the skin on the elbows is naturally hyperpigmented in most people. For the remainder of
the study, all grading and measurements of the psoriatic plaques will be completed by a
blinded investigator who is unaware of which plaque is receiving which treatment. An
unblinded investigator will complete all other portions of the study visit, including digital
photography, injecting the plaques, and completing the biopsies. The subject will also be
blinded as to which plaque is being injected with which treatment.
During the first 4 visits, plaques will be injected with 1-mL of Hylenex® or 1-mL of sterile
(pharmaceutical grade) normal saline (NS). 1-mL of Hylenex® contains 150 Units of recombinant
hyaluronidase. This is the standard dose of the drug that has been approved by the FDA, and
therefore this dose is considered to be safe for use in adults. If injected subcutaneously
into the center of a psoriatic plaque that is between 2 and 5 centimeters in diameter, this
1-mL dose should be able to diffuse throughout the entire area beneath the plaque. The exact
pharmacokinetics of Hylenex® are difficult to study due to its rapid inactivation after
intravenous injection. According to the Hylenex® package insert, though, disruptions to the
dermal barrier that occur in response to subcutaneous Hylenex® injection persist 24 hours
after injection, but this barrier is completely restored after 48 hours. Cutaneous dendritic
cells residing in the epidermis are thought to migrate away from the epidermis through either
lymphatic or vascular channels after Hylenex® is injected. This process should take a few
hours. Since cutaneous dendritic cells are thought to turnover only every several weeks, new
dendritic cells should not populate the epidermis before patients receive the next injection
of Hylenex®. Since dendritic cell activation initiates the inflammatory cascade thought to
result in psoriasis, preventing dendritic cells from being harbored in the epidermis should
essentially prevent the inflammatory cascade that results in psoriasis. Therefore, during the
month-long period while patients are receiving Hylenex® injections, the inflammatory cascade
triggering their psoriasis will potentially be turned off, allowing affected plaques to heal
without propagation of further psoriasis. If this is true, there should be differences in the
Hylenex®-treated versus the NS-treated plaques both morphologically and histologically upon
completion of the final set of biopsies on the Visit 5.
Inclusion Criteria:
- Diagnosis of plaque psoriasis for at least 6 months, with at least 2 psoriatic plaques
on different parts of the body that are both between 2-cm and 5-cm in diameter at the
time of screening
- Age 18-65 years
- Male subjects who agree to use barrier methods for contraception throughout the course
of the trial if their female partners are of child-bearing potential, or female
subjects not of child-bearing potential
- Subject agrees to comply with study requirements
- Subject is fluent in English and is able to provide written informed consent
Exclusion Criteria:
- Subjects with severe medical condition(s) that in the view of the investigator
prohibits participation in the study
- Subject has Netherton's syndrome or other genodermatoses that result in a defective
epidermal barrier
- Subjects who have applied topical medications (prescription or over-the-counter) for
the treatment of psoriasis to their body within 7 days of the baseline visit
- Subjects who have taken cyclosporine, methotrexate, immuran, oral retinoids,
chemotherapeutic agents, anti-inflammatory biologics (e.g., alefacept, etanercept,
etc.), or oral calcineurin inhibitors within 28 days of the baseline visit
- Subjects who are unable to hold their current psoriasis medications for the period of
time indicated (at least 7 days for topical medications, at least 28 days for oral or
injectable medications) without significant worsening of their psoriasis
- Immunocompromised subjects (e.g., lymphoma, HIV/AIDS, Wiskott-Aldrich Syndrome), or
subjects with a history of malignant disease (excluding non-melanoma skin cancer) as
determined by the participant's medical history.
- Subjects receiving phototherapy (e.g., ultraviolet light B [UVB], psoralen plus
ultraviolet light A [PUVA]) within 28 days of the baseline visit
- Subjects with a history of psychiatric disease or history of alcohol or drug abuse
that would interfere with the ability to comply with the study protocol
- Subjects with significant concurrent medical condition(s) at screening that in the
view of the investigator prohibits participation in the study (e.g., severe concurrent
allergic disease, condition associated with malignancy, and condition associated with
immunosuppression)
- Subjects who have used any systemic antibiotics within 28 days of the baseline visit
- Subjects with an active bacterial, viral or fungal skin infection (excluding nail
fungus)
- Subjects currently receiving lithium or have received lithium within the last 4 weeks.
- Ongoing participation in an investigational drug trial
- Subjects with diabetes requiring medication
- Presence of psoriasis with exfoliative erythroderma or presence of guttate psoriasis,
primary palmoplantar psoriasis, or pustular psoriasis
- Hypersensitivity to hyaluronidase or any other ingredient in the formulation of
hyaluronidase, as well as subjects with an allergy or hypersensitivity to lidocaine
- Subjects taking furosemide, benzodiazepines, phenytoin, salicylates, cortisone,
antihistamines or estrogens
We found this trial at
1
site
San Diego, California 92122
Principal Investigator: Tissa Hata, MD
Phone: 858-657-8390
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