Assessing the Efficacy and Safety of Metformin in Treatment of Moderate Psoriasis

Phase 3

• Conditions: Psoriasis
• Interventions: Drug: Metformin; Drug: Placebo; Drug: Topical Coal tar; Drug: Topical calcipotriol

• Registration Number: NCT02644954
• Lead Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh

Brief Summary

Psoriasis vulgaris is a common, chronic, relapsing skin disease characterized by predominant involvement of skin, nails and joints. Recent advances in its patho-physiology have shifted the notion of psoriasis from that of a 'disease of the skin' to a 'T-cell mediated systemic disease'. Better understanding of its pathogenesis and co-morbidities along with the development of novel therapeutics like biological response modifiers has changed the way dermatologists approach the management of psoriasis. Based on the extent of involvement and effect on the quality of life, psoriasis may be mild to moderate in severity. This in turn forms the basis of treatment in majority of the patients. Topical therapies like coal tar, calcipotriol and corticosteroids are sufficient for mild and localized psoriasis. In more widespread or severe forms that are associated with significant decrease in quality of life of patient, phototherapy and systemic therapies are indicated either alone or in combination with each other. Although the introduction of biological therapies has revolutionized the treatment of psoriasis in recent years, such newer therapeutic options continue to elude the vast majority of patients in the developing and under developed world where the traditional agents like methotrexate, cyclosporine, acitretin and phototherapy still form the backbone of treatment.

The association of psoriasis with metabolic syndrome is now well documented. Metabolic syndrome is a cluster of risk factors including central obesity, atherogenic dyslipidemia, hypertension and glucose intolerance and is a strong predictor of cardiovascular diseases, diabetes and stroke. Metformin, an oral hypoglycemic agent of biguanide class is known for its multitude of action on various facets of metabolic syndrome. Recently it has also been found to inhibit keratinocyte proliferation in cell culture model of psoriasis.

The present study is designed as a randomized controlled double blind pilot study in which 40 patients with chronic plaque psoriasis of moderate severity (PASI ≥ 6 or DLQI ≥ 6) and metabolic syndrome (By modified ATP III criteria)4 or impaired glucose tolerance (defined as two-hour glucose levels of 140 to 199 mg per dL on the 75-g oral glucose tolerance test) will be recruited and randomized into two arms, A and B of 20 each, by using random number tables. Patients in arm A will be treated with topical anti-psoriatic treatment (including coal tar and vitamin D3 analogues only) and oral metformin 1g/day 850mg twice daily and patients in arm B will be treated with topical anti-psoriatic treatment and oral placebo tablets. Post randomization patients will be followed up at regular intervals for 24 weeks. During each visit, patients in both arms will be assessed for the severity of psoriasis by psoriasis activity severity index (PASI) and body mass index (BMI). Fasting blood glucose and insulin level, glycosylated haemoglobin (HbA1c) and parameters of metabolic syndrome (including waist circumference, fasting lipid profile and blood pressure) will be assessed at baseline and again at week 16 and 24. The primary aim of this study is to assess the efficacy and safety of oral metformin as an add on therapy for the treatment of chronic plaque psoriasis of moderate severity. The secondary aim is to assess the effect of metformin on parameters of the metabolic syndrome.

Detailed Description

Not available

Study Timeline

• Status Verified: 2015-12
• Study First Submitted: 2015-12-22
• Study First Submitted QC: 2015-12-31
• Last Update Submitted: 2015-12-31
• Study Start: 2016-01
• Study First Posted: 2016-01-01
• Last Update Posted: 2016-01-01
• Primary Completion: 2016-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Chronic plaque psoriasis of moderate severity, defined as PASI ≥ 6 and/or DLQI ≥ 6
• Metabolic syndrome (By modified ATP III criteria)4 or impaired glucose tolerance (defined as two-hour glucose levels of 140 to 199 mg per dL on the 75-g oral glucose tolerance test.)

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Exclusion Criteria

• Known drug allergies to biguanides.
• Psoriatic arthritis
• Pustular psoriasis
• Severe psoriasis PASI>10, DLQI> 10
• Patient with overt diabetes mellitus, defined as fasting blood sugar > 126mg/dl glucose tolerance test of >200mg/dl.
• Intake of oral hypoglycemic or systemic anti-psoriatic medication within the last 4 weeks.
• Patients on medications for cardiovascular, gastrointestinal, hepatic, renal, disorders

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin	Metformin	Topical coal tar and topical calcipotriol + oral metformin 850mg twice daily
Metformin	Topical Coal tar	Topical coal tar and topical calcipotriol + oral metformin 850mg twice daily
Metformin	Topical calcipotriol	Topical coal tar and topical calcipotriol + oral metformin 850mg twice daily
Placebo	Placebo	Topical coal tar and topical calcipotriol
Placebo	Topical Coal tar	Topical coal tar and topical calcipotriol
Placebo	Topical calcipotriol	Topical coal tar and topical calcipotriol

Primary Outcome Measures

Name	Time	Method
The proportion of patients achieving 75% reduction in psoriasis activity severity index (PASI)	1 year	Evaluate the efficacy of oral metformin in chronic plaque psoriasis of moderate severity. The proportion of patients achieving PASI 75 assesses the efficacy.

Secondary Outcome Measures

Name	Time	Method
The number of patients who show change in parameters of metabolic syndrome after taking metformin	1 year
The proportion of patients achieving 90% reduction in psoriasis activity severity index (PASI)	1 year