PsoriasisNCT00470392
Mechanistically-based Optimization of UV Radiation Therapy in Psoriasis
A study testing Imiquimod and Clobetasol in people with Psoriasis, run by VA Office of Research and Development at 2 sites in United States.
Trial summary
The purpose of this study is 1) to determine whether Imiquimod or Steroid pretreatment modifies UVB laser light response resulting in increased cell death compared to UVB laser light alone; 2) to determine if pretreatment of psoriatic lesions with Imiquimod or Steroid prior to UVB laser light exposure selectively… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Psoriasis
- What is being tested?
- Imiquimod and Clobetasol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2007to Jul 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The presence of plaque-type psoriasis in areas of the trunk, buttocks, or extremities that are amenable to biopsy and evaluable disease in at least 2 cm target treatment sites separated by 1 cm
- Age 18-80, both genders, all ethnicities
- No contraindications to phototherapy or biopsy procedures
- No topical steroid, tar, phototherapy, Vitamin D, or retinoid therapy to target lesions for at least 1 week prior to the study
- No systemic psoriasis therapy for at least four weeks prior to the study
- Able to give informed consent under IRB approval procedures
Who cannot join
- Photosensitivity disorders
- Active untreated diseases or medication usage which may interfere with UVB, wound healing, or immune function
- Hypersensitivity to local anesthetic
- Inability to provide informed consent
- Pregnancy and /or lactating
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University Hospital Case Medical Center
Cleveland, Ohio, 44106
VA Medical Center, Cleveland
Cleveland, Ohio, 44106
About this study
The purpose of this study is 1) to determine whether Imiquimod or Steroid pretreatment modifies UVB laser light response resulting in increased cell death compared to UVB laser light alone; 2) to determine if pretreatment of psoriatic lesions with Imiquimod or Steroid prior to UVB laser light exposure selectively effects various T cell functions; 3) to determine clinical results from the Imiquimod/Steroid/UVB laser light and correlate those changes with immuno-histochemical changes in the skin; and 4) to determine if single high dose lesion limited UVB laser light intervention combined with Imiquimod or Steroid influences T cell changes
Read the detailed description
The characteristic lesion of psoriasis is a sharply demarcated erythematous papule or plaque with excessive scaling due to hyperproliferating keratinocytes, infiltrating granulocytes, and a dense mononuclear infiltrate with activated T cells. To date, no one mechanism has been explanatory for the panoply of changes that occur in both the dermis and epidermis of psoriasis patients. Several key findings have shown that cutaneous T cells play a key role in the propagation of the disease; memory-type T cells home to the skin, specifically due to expression of cutaneous lymphocyte antigen (CLA), and are the main effector cells in psoriatic tissue responsible for the production of cytokines that result in exacerbated cutaneous inflammation. T cell recruitment is thought to occur in psoriasis, in part, as a result of cytokine and chemokine release from keratinocytes, macrophages, and endothelial cells. CLA-positive T cells migrate into the tissues where memory-effector T cells are activated and expand. This migration is critical to maintenance of the psoriasis lesions, because anti-LFA-1 antibodies (efalizumab) are effective in treating psoriasis, resulting in blood lymphocytosis and tissue depletion of T cells. Despite many years of using UVB phototherapy in the treatment of psoriasis, its mechanism of action is based mainly on in vitro exposures of isolated cells and on extrapolations from UV effects on normal skin, with little direct data from lesional skin.
Previously, our studies determined optimal single efficacious dose using the Excimer laser, refined the mechanism of UVB action in psoriasis, developed key cytokine quantitative meth -ods to assess targeted mRNA levels in psoriatic tissue after treatment, demonstrated that regulatory T cells from psoriasis tissue and blood appear to have a functional defect, and demonstrated that UVA component of solar radiation is a critical and significant contributor to UV-induced in vivo immuno-suppression. All of these previous findings lead us to our current hypothesis that direct selective apoptotic effects on the T mem/Teff cells may result in decreased APC activation and IL-12 over-riding of Treg suppression and a re-balanced Tre:Tmem/eff cell ratio which in turn may have a sustained remittive effect (high duration multi-month clearing of a psoriasis lesion after a single UVB laser light treatment.)
- Conditions
- Psoriasis
- Being tested
- Imiquimod, Clobetasol
- Keywords
- Erythema, optimization, Papule, Plaque, pretreatment, T cells, UVB laser light, psoriasis, topical administration
- Medical subject headings
- Psoriasis, Erythema, Plaque, Amyloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImiquimodDrug
Also called Aldara
Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Imiquimod (5% topical cream) was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.
ClobetasolDrug
Also called Temovate
Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Clobetasol propionate 0.05% was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.
| Study group | Role | What they receive |
|---|---|---|
| Imiquimod | Other | Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Imiquimod (5% topical cream) was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point. Receives: Drug: Imiquimod |
| Clobetasol | Other | Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Clobetasol propionate 0.05% was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point. Receives: Drug: Clobetasol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Elevated MyxA
Lesions were treated with either Imiquimod or Clobetasol cream. Lesions were subsequently treated with UVB and biopsied. From the biopsy samples obtained from the Imiquimod arm, quantitative PCR was performed to measure levels of Myx A, an imiquimod response gene.
Measured: Biopsy samples for analysis were taken 1 hour post UVB treatment
Secondary outcomes (2)
Number of Subjects With Improvement in Lesional Psoriasis Area and Assessment (PASI) Score After Imiquimod and UVB Treatment
The PASI is a disease burden measure that integrates area, erythema, thickness and scale of each target lesion. The severity score for each region is calculated by adding the scores for redness, thickness and scale (each of which are graded from 0 to 4). The maximum severity score is 12. The higher the PASI, the worse the disease. Thus, an improvement in PASI score is a lower score than the pre-treatment PASI.
Measured: 2 weeks after Imiquimod and UVB
Number of Subjects With a 1.5 Fold Increase in mRNA Expression of GRAMD1A and DMXL2
Based upon upregulated mRNA expression of MyxA in 1 out of 7 patients treated with Imiquimod, a list of alternative target genes responsive to Imiquimod was generated. The target mRNAs examined included GRAMD1A, IL2RA, TGHD1, DMXL2. The target gene was consider upregulated if there was a 1.5 fold increase in the mRNA expression of the target gene.
Measured: Biopsy samples for analysis were taken 1 hour post UVB treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2007 (estimated)
- Study startMay 2007
- Primary completionJul 2010
- Study completionJul 2012
Why it stopped: Recruiting complete and administrative termination
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PsoriasisStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- University Hospitals Cleveland Medical Center
- Responsible party
- Sponsor
- Investigators
- Kevin D Cooper, MD, Principal investigator, VA Medical Center-Cleveland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00470392
- Sponsor's protocol ID
- IMMB-004-06S
- Status last verified
- Oct 2016
- First submitted
- 4 May 2007
- Last updated
- 5 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistically-based Optimization of UV Radiation Therapy in Psoriasis
- ClinicalTrials.gov ID
- NCT00470392
- Acronym / sponsor ID
- IMMB-004-06S
- Conditions
- Psoriasis
- Keywords
- Erythema, optimization, Papule, Plaque, pretreatment, T cells, UVB laser light, psoriasis
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruiting complete and administrative termination
- Enrolment
- 9 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- University Hospitals Cleveland Medical Center
- Study start
- May 2007
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 7 May 2007 (estimated)
- Results
- Posted 12 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is 1) to determine whether Imiquimod or Steroid pretreatment modifies UVB laser light response resulting in increased cell death compared to UVB laser light alone; 2) to determine if pretreatment of psoriatic lesions with Imiquimod or Steroid prior to UVB laser light exposure selectively effects various T cell functions; 3) to determine clinical results from the Imiquimod/Steroid/UVB laser light and correlate those changes with immuno-histochemical changes in the skin; and 4) to determine if single high dose lesion limited UVB laser light intervention combined with Imiquimod or Steroid influences T cell changes
Detailed description
The characteristic lesion of psoriasis is a sharply demarcated erythematous papule or plaque with excessive scaling due to hyperproliferating keratinocytes, infiltrating granulocytes, and a dense mononuclear infiltrate with activated T cells. To date, no one mechanism has been explanatory for the panoply of changes that occur in both the dermis and epidermis of psoriasis patients. Several key findings have shown that cutaneous T cells play a key role in the propagation of the disease; memory-type T cells home to the skin, specifically due to expression of cutaneous lymphocyte antigen (CLA), and are the main effector cells in psoriatic tissue responsible for the production of cytokines that result in exacerbated cutaneous inflammation. T cell recruitment is thought to occur in psoriasis, in part, as a result of cytokine and chemokine release from keratinocytes, macrophages, and endothelial cells. CLA-positive T cells migrate into the tissues where memory-effector T cells are activated and expand. This migration is critical to maintenance of the psoriasis lesions, because anti-LFA-1 antibodies (efalizumab) are effective in treating psoriasis, resulting in blood lymphocytosis and tissue depletion of T cells. Despite many years of using UVB phototherapy in the treatment of psoriasis, its mechanism of action is based mainly on in vitro exposures of isolated cells and on extrapolations from UV effects on normal skin, with little direct data from lesional skin.
Previously, our studies determined optimal single efficacious dose using the Excimer laser, refined the mechanism of UVB action in psoriasis, developed key cytokine quantitative meth -ods to assess targeted mRNA levels in psoriatic tissue after treatment, demonstrated that regulatory T cells from psoriasis tissue and blood appear to have a functional defect, and demonstrated that UVA component of solar radiation is a critical and significant contributor to UV-induced in vivo immuno-suppression. All of these previous findings lead us to our current hypothesis that direct selective apoptotic effects on the T mem/Teff cells may result in decreased APC activation and IL-12 over-riding of Treg suppression and a re-balanced Tre:Tmem/eff cell ratio which in turn may have a sustained remittive effect (high duration multi-month clearing of a psoriasis lesion after a single UVB laser light treatment.)
Study design
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Imiquimod | Other | Drug: ImiquimodEach study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Imiquimod (5% topical cream) was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point. |
| Clobetasol | Other | Drug: ClobetasolEach study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Clobetasol propionate 0.05% was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- The presence of plaque-type psoriasis in areas of the trunk, buttocks, or extremities that are amenable to biopsy and evaluable disease in at least 2 cm target treatment sites separated by 1 cm
- Age 18-80, both genders, all ethnicities
- No contraindications to phototherapy or biopsy procedures
- No topical steroid, tar, phototherapy, Vitamin D, or retinoid therapy to target lesions for at least 1 week prior to the study
- No systemic psoriasis therapy for at least four weeks prior to the study
Key exclusion criteria (5 listed)
- Photosensitivity disorders
- Active untreated diseases or medication usage which may interfere with UVB, wound healing, or immune function
- Hypersensitivity to local anesthetic
- Inability to provide informed consent
- Pregnancy and /or lactating
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImiquimodAlso: AldaraEach study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Imiquimod (5% topical cream) was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point. | Drug | Imiquimod |
| ClobetasolAlso: TemovateEach study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Clobetasol propionate 0.05% was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point. | Drug | Clobetasol |
Primary outcome
Number of Subjects With Elevated MyxA
Time frame: Biopsy samples for analysis were taken 1 hour post UVB treatment
Lesions were treated with either Imiquimod or Clobetasol cream. Lesions were subsequently treated with UVB and biopsied. From the biopsy samples obtained from the Imiquimod arm, quantitative PCR was performed to measure levels of Myx A, an imiquimod response gene.
2 secondary outcomes
Number of Subjects With Improvement in Lesional Psoriasis Area and Assessment (PASI) Score After Imiquimod and UVB Treatment
Time frame: 2 weeks after Imiquimod and UVB
Number of Subjects With a 1.5 Fold Increase in mRNA Expression of GRAMD1A and DMXL2
Time frame: Biopsy samples for analysis were taken 1 hour post UVB treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The National Institute of Arthritis, Musculoskeletal, and Skin Diseases website providing fast facts on health topics, including psoriasisLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin D Cooper, MD principal investigator
VA Medical Center-Cleveland
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Imiquimod and Clobetasol in people with Psoriasis, run by VA Office of Research and Development at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Elevated MyxA (time frame: Biopsy samples for analysis were taken 1 hour post UVB treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2016.