Clinical trial NCT02432040: Efficacy of Atorvastatin as Adjunctive Treatment for Chronic Plaque Type Psoriasis
Official title: Atorvastatin as Adjunctive Therapy for Chronic Plaque Type Psoriasis Versus Betamethasone Valerate Alone:A Randomized, Double-Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis
Keywords: chronic plaque psoriasis
psoriasis
atorvastatin
psoriasis area and severity index
betamethasone valerate
Lead sponsor: Philippine Dermatological Society
Sponsor class: NETWORK
First posted: 2015-05-01
Enrollment: 28
Sex: ALL
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aimed to assess the efficacy and safety of atorvastatin 40 mg/day as an adjunct to betamethasone valerate 0.1% ointment applied twice daily in the treatment of patients with mild to moderate chronic plaque type psoriasis, as determined by mean reduction in PASI scores. Specific objectives included the determination and comparison of the absolute number and proportion of patients who achieved PASI-50 and the mean reductions in lipid profile (total cholesterol, HDL, LDL, triglycerides) and high-sensitivity C-reactive protein (hsCRP) measured from baseline and every month thereafter up to 6 months of treatment. This study also investigated the impact of atorvastatin treatment on the patients' quality of life as well as the association of clinical response to the lipid-lowering and anti-inflammatory effects of atorvastatin.

Detailed description: This was a single-center, parallel-group, randomized, double-blind, placebo-controlled clinical trial. The study was conducted from February 2013 to October 2013 at a dermatology out-patient clinic in a tertiary hospital in the Philippines. Twenty-eight patients aged 19-65 years old assessed to have mild to moderate chronic plaque psoriasis, with psoriasis area and severity index (PASI) scores less than 10, were enrolled into the study and randomized into two equal treatment groups. Before participating in the study, patients were required to have a washout period of psoriasis pharmacotherapy for at least 2 months for phototherapy and systemic drugs, and 2 weeks for topical therapies.

Exclusion criteria were as follows: patients with uncontrolled hypertension, endocrine or other metabolic diseases; patients with known allergy to any of the treatments; patients with active liver disease or liver enzymes (AST and ALT) thrice the upper limit; patients with any myopathy or presence of elevated creatine kinase (CK-MM) levels; patients taking any drug that might interact with statins and those already taking statins or patients with clear indications for statin treatment; patients with impaired renal function or creatinine \> 2.0 mg/dL; patients with active infection or white blood cell (WBC) \> 10 and pregnant or lactating females. The study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee. Informed consent was obtained from all participants at study entry.

Patients were randomly assigned into the two groups through a computer-generated randomization table with sequencing of assignments unknown to the primary investigator. The assigned interventions were placed in sequentially-numbered, opaque envelopes, which were opened by one of the secondary investigators only after the patient had agreed to participate in the study. Patients were assigned numerical codes that were indicated in their case record forms.

Fourteen patients took atorvastatin 40 mg once a day while 14 patients took a similar-looking placebo tablet once a day. The study duration was 6 months. All patients were allowed to continue the use of betamethasone valerate 0.1% ointment twice a day for the duration of the study. Dispensing of the medications was done by a secondary investigator, while clinical assessment was done by the primary investigator who was blinded to the treatment assignments.

Patients' PASI scores, lipid profiles, aspartate aminotransferase (AST), alanine aminotransferase (ALT), hsCRP levels, and dermatology life and quality index (DLQI) scores were taken at baseline. Recording of the lipid profile, and AST, ALT values was done by another secondary investigator so that the primary investigator would not be biased by the decreasing values of the lipid profile or elevations in the AST or ALT. Photo-documentation was done throughout the study. Patients were also asked to bring their medications each visit so that the primary investigator could check for compliance. PASI scores, lipid profiles, AST, and ALT levels were monitored monthly, while DLQI scores and hsCRP levels were evaluated again after 6 months of therapy. Difference in the mean changes in PASI scores, lipid profile levels, DLQI scores, and hsCRP levels between groups were compared. Difference in the proportion of patients reaching 50% reduction in PASI scores (PASI-50) after 3 months and that after 6 months of therapy were compared. Correlation between the changes in PASI scores and the changes in lipid profile levels, as well as correlation between the changes in PASI scores and the changes in hsCRP levels were computed.

The period of observation for adverse events started from the time the subject received the first dose of the study drug until his last follow-up. Adverse event monitoring was by active query and spontaneous reporting.

Intention-to-treat analysis was the primary efficacy analysis. Patients included were those who had at least one assessment beyond baseline (Month 1). The last measurement of each randomized patient was moved forward to represent the end-of-treatment measurement at 6 months. Per-protocol analysis was the secondary efficacy analysis. All data analyses were performed using a statistical software (STATA 12.0).

Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with mild to moderate psoriasis vulgaris, chronic plaque type, with PASI score not more than 10
* Adult patients ≥ 19 years old and ≤ 65 years old
* Male or female
* Able to give consent
* Able to follow-up monthly for 6 months

Exclusion Criteria:

* Patients with PASI score ≥ 10
* Systemic therapy for psoriasis within the last two months
* Phototherapy within the last four weeks
* Known allergy to any of the treatments
* Active liver disease or liver enzymes (AST and ALT) more than 3 times the upper limit of normal
* Any myopathy or presence of elevated creatine kinase (CK-MM) levels
* Intake of any drug that might affect or interact with the study drug (e.g. fibrates, niacin, macrolide antibiotics)
* Patients already taking statins or patients with clear indications for statin treatment (i.e. coronary heart disease or disease equivalents according to the Adult Treatment Panel III Guidelines)
* Impaired renal function or creatinine \> 2.0 mg/dL
* Active infection or WBC \> 10
* Pregnant or lactating
* Uncontrolled hypertension, endocrine or other metabolic diseases

Primary outcomes:
measure: Mean Gross Change in Psoriasis Area and Severity Index (PASI) Scores From Baseline to the End of 6 Months
timeFrame: 6 months
measure: Percentage of Patients Achieving PASI-50 in Each Arm at the End of 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Monthly Mean Changes in PASI Scores
timeFrame: Monthly from baseline to 6 months
measure: Percentage of Patients Achieving PASI-50 at the End of 3 Months
timeFrame: 3 months
measure: Mean Change in Dermatology Life Quality Index (DLQI) Scores After 6 Months
timeFrame: 6 months
measure: Mean Change in Lipid Profile Levels
timeFrame: 6 months
measure: Mean Change in hsCRP Levels
timeFrame: 6 months
measure: Adverse Events
timeFrame: 6 months
Other outcomes:
Locations:
city: Manila
country: Philippines
facility: University of the Philippines - Philippine General Hospital Section of Dermatology
Study officials:
affiliation: University of the Philippines-Philippine General Hospital Section of Dermatology
name: Sharlene H Chua, Medicine
role: PRINCIPAL_INVESTIGATOR
affiliation: University of the Philippines-Philippine General Hospital Section of Dermatology
name: Ma. Lorna F Frez, Medicine
role: STUDY_DIRECTOR
References: