Efficacy of Atorvastatin as Adjunctive Treatment for Chronic Plaque Type Psoriasis

• Sponsor: Philippine Dermatological Society (Other)
• Overall Status: Completed
• CT.gov ID: NCT02432040
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 3.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: Atorvastatin; Drug: Placebo	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Atorvastatin as Adjunctive Therapy for Chronic Plaque Type Psoriasis Versus Betamethasone Valerate Alone:A Randomized, Double-Blind, Placebo-Controlled Trial
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atorvastatin Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most	Drug: Atorvastatin; Atorvastatin is a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor used to treat dyslipidemia; Other Names: Atopitar
Placebo Comparator: Placebo Placebo tablets But patients are still asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most	Drug: Placebo; Placebo tablets, made to look like the interventional drug

Outcome Measures

Primary Outcome Measures

1. Mean Gross Change in Psoriasis Area and Severity Index (PASI) Scores From Baseline to the End of 6 Months [6 months]

   Psoriasis Area and Severity Index involves grading psoriatic plaques based on erythema (E), infiltration (I), desquamation (D). Severity is graded from 0-4 for each criteria (0 - none, 1 - slight, 2 - moderate, 3 - severe, and 4 - very severe). The body is divided into 4 regions, head, upper extremities, trunk, and lower extremities, and for each region, the surface area involvement is graded on a 0-6 scale (0 - 0% involvement, 1 - <10%, 2 - 10-<30%, 3 - 30-<50%, 4 - 50-<70%, 5 - 70-<90%, 6 - 90-100%).The highest potential PASI score is 72, with higher PASI scores indicating worse psoriasis.

2. Percentage of Patients Achieving PASI-50 in Each Arm at the End of 6 Months [6 months]

   Percentage of patients in each arm who will achieve 50% reduction in PASI scores at the end of 6 months will be compared

Secondary Outcome Measures

1. Monthly Mean Changes in PASI Scores [Monthly from baseline to 6 months]

   PASI scores were measured monthly and mean changes from baseline for each month for the whole 6-month duration of the study recorded.

2. Percentage of Patients Achieving PASI-50 at the End of 3 Months [3 months]

   PASI-50 means at least a 50% reduction from baseline PASI score

3. Mean Change in Dermatology Life Quality Index (DLQI) Scores After 6 Months [6 months]

4. Mean Change in Lipid Profile Levels [6 months]

5. Mean Change in hsCRP Levels [6 months]

6. Adverse Events [6 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of the Philippines - Philippine General Hospital Section of Dermatology	Manila		Philippines	1000

Sponsors and Collaborators

• Philippine Dermatological Society

Investigators

• Principal Investigator: Sharlene H Chua, Medicine, University of the Philippines-Philippine General Hospital Section of Dermatology
• Study Director: Ma. Lorna F Frez, Medicine, University of the Philippines-Philippine General Hospital Section of Dermatology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sharlene Chua, Dr., Philippine Dermatological Society
• ClinicalTrials.gov Identifier: NCT02432040
• Other Study ID Numbers: PDS_PGH_2013_002
• First Posted: May 1, 2015
• Last Update Posted: Nov 23, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Sharlene Chua, Dr., Philippine Dermatological Society: chronic plaque psoriasis; psoriasis; atorvastatin; psoriasis area and severity index; betamethasone valerate
• Additional relevant MeSH terms: Psoriasis; Atorvastatin

Study Results

Participant Flow

Recruitment Details	The study was conducted from February 2013 to October 2013 at a dermatology out-patient clinic in a tertiary hospital in the Philippines. Patients diagnosed with mild to moderate chronic plaque type psoriasis were screened for eligibility.
Pre-assignment Detail	Patients who were not newly diagnosed with psoriasis and already on medications were allowed to be enrolled into the study as long as they have been free of any systemic anti-psoriatic therapy for at least 2 months or free from topical steroids for at least 2 weeks.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most Atorvastatin: Atorvastatin is an HMG-CoA reductase inhibitor used to treat dyslipidemia	Placebo tablets Patients are asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most
Period Title: Overall Study
STARTED	14	14
COMPLETED	6	8
NOT COMPLETED	8	6

Baseline Characteristics

Arm/Group Title	Atorvastatin	Placebo	Total
Arm/Group Description	Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most Atorvastatin: Atorvastatin is an HMG-CoA reductase inhibitor used to treat dyslipidemia	Placebo tablets But patients are still asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most	Total of all reporting groups
Overall Participants	14	14	28
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	41.29 (11.38)	40.71 (12.00)	41 (11.48)
Sex: Female, Male (Count of Participants)
Female	7 50%	10 71.4%	17 60.7%
Male	7 50%	4 28.6%	11 39.3%
PASI score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.49 (2.78)	5.63 (2.52)	5.56 (2.61)
Total cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	193.02 (34.85)	197.73 (36.52)	195.37 (35.11)
Triglycerides (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	126.73 (45.71)	112.27 (45.37)	119.50 (45.29)
LDL-cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	125.88 (29.42)	129.49 (29.11)	127.69 (28.78)
HDL-cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	46.13 (12.68)	46.56 (13.13)	46.34 (12.67)
High-sensitivity C-reactive protein (hsCRP) (nmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [nmol/L]	63.46 (119.43)	39.62 (44.67)	51.54 (89.31)
DLQI score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	11.50 (6.04)	9.07 (5.84)	10.29 (5.96)

Outcome Measures

1. Primary Outcome

Title	Mean Gross Change in Psoriasis Area and Severity Index (PASI) Scores From Baseline to the End of 6 Months
Description	Psoriasis Area and Severity Index involves grading psoriatic plaques based on erythema (E), infiltration (I), desquamation (D). Severity is graded from 0-4 for each criteria (0 - none, 1 - slight, 2 - moderate, 3 - severe, and 4 - very severe). The body is divided into 4 regions, head, upper extremities, trunk, and lower extremities, and for each region, the surface area involvement is graded on a 0-6 scale (0 - 0% involvement, 1 - <10%, 2 - 10-<30%, 3 - 30-<50%, 4 - 50-<70%, 5 - 70-<90%, 6 - 90-100%).The highest potential PASI score is 72, with higher PASI scores indicating worse psoriasis.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Intention-to-treat analysis was done. Patients with a baseline score and who had at least one reading after baseline were included.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most Atorvastatin: Atorvastatin is an HMG-CoA reductase inhibitor used to treat dyslipidemia	Placebo tablets Patients are asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most
Measure Participants	11	11
Mean (Standard Deviation) [units on a scale]	-2.15 (2.17)	-1.69 (2.36)

2. Primary Outcome

Title	Percentage of Patients Achieving PASI-50 in Each Arm at the End of 6 Months
Description	Percentage of patients in each arm who will achieve 50% reduction in PASI scores at the end of 6 months will be compared
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Intention-to-treat analysis was done. Patients with a baseline score and who had at least one reading after baseline were included.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most Atorvastatin: Atorvastatin is an HMG-CoA reductase inhibitor used to treat dyslipidemia	Placebo tablets Patients are asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most
Measure Participants	11	11
Number [percentage of participants]	27.3 195%	45.5 325%

3. Secondary Outcome

Title	Monthly Mean Changes in PASI Scores
Description	PASI scores were measured monthly and mean changes from baseline for each month for the whole 6-month duration of the study recorded.
Time Frame	Monthly from baseline to 6 months

Outcome Measure Data

Analysis Population Description

Intention-to-treat analysis was done. Patients with a baseline score and who had at least one reading after baseline were included.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most Atorvastatin: Atorvastatin is an HMG-CoA reductase inhibitor used to treat dyslipidemia	Placebo tablets Patients are asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most
Measure Participants	11	11
Mean change for the first month	-0.72 (0.63)	-0.71 (0.88)
Mean change for the second month	-1.67 (1.99)	-0.69 (1.00)
Mean change for the third month	-2.19 (2.27)	-1.16 (1.52)
Mean change for the fourth month	-2.10 (2.20)	-1.13 (2.05)
Mean change for the fifth month	-2.15 (2.16)	-1.43 (2.59)
Mean change for the sixth month	-2.15 (2.17)	-1.69 (2.36)

4. Secondary Outcome

Title	Percentage of Patients Achieving PASI-50 at the End of 3 Months
Description	PASI-50 means at least a 50% reduction from baseline PASI score
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Intention-to-treat analysis was done. Patients with a baseline score and who had at least one reading after baseline were included.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most Atorvastatin: Atorvastatin is an HMG-CoA reductase inhibitor used to treat dyslipidemia	Placebo tablets Patients are asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most
Measure Participants	11	11
Number [percentage of participants]	36.4 260%	18.2 130%

5. Secondary Outcome

Title	Mean Change in Dermatology Life Quality Index (DLQI) Scores After 6 Months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The number of patients analyzed were the ones who completed the study. Intention-to-treat analysis was done.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most Atorvastatin: Atorvastatin is an HMG-CoA reductase inhibitor used to treat dyslipidemia	Placebo tablets Patients are asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most
Measure Participants	6	8
Mean (Standard Deviation) [units on a scale]	-6.5 (5.58)	-2.13 (6.56)

6. Secondary Outcome

Title	Mean Change in Lipid Profile Levels
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Intention-to-treat analysis was done. Patients who completed the study were included.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most Atorvastatin: Atorvastatin is an HMG-CoA reductase inhibitor used to treat dyslipidemia	Placebo tablets Patients are asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most
Measure Participants	6	8
Total cholesterol	-35.39 (47.94)	-38.32 (74.72)
Triglycerides	-17.55 (49.93)	-5.12 (39.35)
LDL Cholesterol	-45.18 (24.28)	-13.48 (24.02)
HDL Cholesterol	3.15 (5.95)	-0.69 (11.00)

7. Secondary Outcome

Title	Mean Change in hsCRP Levels
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Intention-to-treat analysis was done. Patients who completed the study were included since they were the only ones who had another hsCRP reading after baseline.

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most Atorvastatin: Atorvastatin is an HMG-CoA reductase inhibitor used to treat dyslipidemia	Placebo tablets Patients are asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most
Measure Participants	6	8
Mean (Standard Deviation) [nmol/L]	-7.58 (32.92)	-5.14 (28.34)

8. Secondary Outcome

Title	Adverse Events
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Atorvastatin	Placebo
Arm/Group Description	Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most Atorvastatin: Atorvastatin is an HMG-CoA reductase inhibitor used to treat dyslipidemia	Placebo tablets Patients are asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most
Measure Participants	14	14
Number [participants]	2 14.3%	0 0%

Adverse Events

Arm/Group Title	Atorvastatin		Placebo
Arm/Group Description	Atorvastatin 40 mg once a day at night Patients asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most Atorvastatin: Atorvastatin is an HMG-CoA reductase inhibitor used to treat dyslipidemia		Placebo tablets Patients are asked to apply Betamethasone valerate 0.1% ointment twice a day, 3 weeks on, 1 week off, at the most
All Cause Mortality
	Atorvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Atorvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Atorvastatin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)		0/14 (0%)
Hepatobiliary disorders
Elevation in liver enzymes	1/14 (7.1%)	2	0/14 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle aches	1/14 (7.1%)	1	0/14 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.