Psoriatic Arthritis Treated With Liraglutide Therapy: a QUality of Life and Efficacy Study (PLAQUE)

July 14, 2017 updated by: University Health Network, Toronto

Clinical Evaluation of Psoriatic Arthritis Treated With Liraglutide. The PLAQUE Study: Psoriatic Arthritis Treated With Liraglutide Therapy: a QUality of Life and Efficacy Study

Exploratory, double-blind randomized, placebo-controlled, Phase II study to evaluate the effect(s) of short-term administration of liraglutide, a GLP-1R (glucagon-like peptide-1 receptor) agonist on joint and skin inflammation in patients with active Psoriatic Arthritis.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The primary purpose of this study is to determine whether short-term (12-week) administration of the GLP-1R agonist, liraglutide, will improve joint and skin swelling in patients with active Psoriatic Arthritis compared to placebo.

Background: Psoriatic Arthritis is a systemic inflammatory T-cell disorder affecting the joints and spine, and is associated with an elevated risk for Type 2 Diabetes and Cardiovascular Disease. In addition to classical effects on glycemic-lowering, GLP-1R agonists are anti-diabetes agents which also have anti-inflammatory properties that may be clinically useful for patients with inflammatory diseases, particularly those with co-morbid metabolic disease. While a few small exploratory studies in patients with psoriasis have demonstrated that GLP-1R agonists reduce the severity of skin plaques, dedicated prospective, randomized mechanistic studies evaluating potential mechanisms by which GLP-1R agonists exert anti-inflammatory action(s) in humans with inflammatory disease is lacking.

Objectives: Primary objective is to evaluate the clinical efficacy of short-term liraglutide (GLP-1R agonist) administration on the severity of joint and skin inflammation in patients with active Psoriatic Arthritis. Secondary objectives are to determine whether short-term liraglutide administration in patients with active psoriatic arthritis will 1) modify the degree of impaired glucose tolerance, underlying b-cell function and cardiovascular risk factor profiles, 2) improve patient-centered outcomes such as quality of life and functionality, 3) modify specific sub-populations of T-cells and affect their differentiation and activation, and 4) modify activation of circulating immune cells, pro-inflammatory cytokines, and hormones.

Design: Double-blind, randomized, placebo-controlled trial, Phase II.

Patient population: 34 patients between with active Psoriatic Arthritis meeting CASPAR (ClASsification criteria for Psoriatic ARthritis).

Intervention: Participants will be randomized (1:1) to liraglutide (1.2 mg sc daily) or to placebo (sc daily) for 12 weeks.

Endpoints: The primary endpoint of this study will be the proportion of patients who experience a 20% ACR (American College of Rheumatology) improvement response following liraglutide therapy as compared to placebo.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5T 2S8
        • Toronto Western Hospital, The Centre for Prognosis Studies in the Rheumatic Diseases (CPSRD), University of Toronto

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with active psoriatic arthritis (3 tender and swollen joints) meeting CASPAR study group criteria

Exclusion Criteria:

  • BMI > 35 kg/m2
  • Uncontrolled diabetes, HbA1c > 10.5%
  • Current biological treatment for any inflammatory disorder within the past three months
  • renal dysfunction (eGFR < 50 ml/min/1.73m or macroalbuminuria >300mg)
  • hepatic dysfunction (AST (aspartate aminotransferase), ALT (alanine aminotransferase), Total bilirubin > 3 times upper limit of normal)
  • history of pancreatitis or personal or family history of medullary thyroid cancer, c-cell hyperplasia, or MEN-2 syndrome
  • current pregnancy or current breast feeding
  • use of DPP-4 (dipeptidyl peptidase-4 inhibitor) or GLP-1 receptor agonist within 2 months (washout is permitted)
  • drug or alcohol dependence
  • resting tachycardia > 100 bpm or conduction abnormalities associated with tachycardia
  • current enrollment in any other clinical trial
  • symptomatic gastroparesis
  • concomitant serious medical conditions
  • all medication for the treatment of Psoriatic Arthritis such as MTX (methotrexate) < 25 mg, LFN (leflunomide) < 20 mg, and NSAIDs (non-steroidal anti-inflammatory drugs) will have been used at stable doses for at least 4 weeks, having been initiated at least 3 months prior to study start (8 weeks before screening, 4 weeks before baseline) for MTX and LFN and at least 4 weeks for NSAIDs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Interventional arm
liraglutide 0.6mg sc daily for 1 week, 1.2mg sc daily for 11 weeks
Drug: liraglutide
Liraglutide 0.6mg sc daily for 1 week, 1.2mg sc daily for 11 weeks
Other Names:
  • Victoza
Placebo Comparator: Placebo arm
Placebo sc daily for 12 weeks, volume titration at week 2 to mirror liraglutide arm
Other: Placebo
Placebo sc daily for 12 weeks, volume titration at week 2 to mirror liraglutide arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The change in the proportion of patients achieving an ACR 20% improvement response in patients with psoriatic arthritis receiving liraglutide for 12 weeks compared to placebo
Time Frame: Baseline to 12 weeks, liraglutide compared to placebo
Proportion of patients achieving an ACR (American College of Rheumatology) 20% improvement response. ACR 20 is a composite rheumatological endpoint which includes swollen joint count, tender joint count, pain, physician global assessment, patient global assessment, HAQ (health assessment questionnaire), CRP (c reactive protein).
Baseline to 12 weeks, liraglutide compared to placebo

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The change in the psoriasis area and severity index (PASI) in patients with psoriatic arthritis receiving liraglutide for 12 weeks compared to those receiving placebo
Time Frame: Baseline to 12 weeks
Baseline to 12 weeks
The change in quality of life measured by validated quality of life questionnaires in patients with psoriatic arthritis receiving liraglutide for 12 weeks compared to those receiving placebo
Time Frame: Baseline to 12 weeks
Baseline to 12 weeks
The change in glucose tolerance in patients with psoriatic arthritis with glucose intolerance at baseline who receive liraglutide for 12 weeks compared to those receiving placebo
Time Frame: Baseline to 12 weeks
Baseline to 12 weeks
The effect(s) of liraglutide on cardiovascular disease risk factors in patients with psoriatic arthritis receiving liraglutide for 12 weeks compared to those receiving placebo
Time Frame: Baseline to 12 weeks
Cardiovascular disease risk factors (Systolic blood pressure, cholesterol profiles, CRP, body weight, waist circumference)
Baseline to 12 weeks
The effect(s) of liraglutide on the enumeration of circulating T-cell subpopulations, and on activation of circulating T-cell subpopulations
Time Frame: Baseline to 12 weeks
Multi-parameter phospho flow cytometry analysis of T-cell differentiation and activation of peripheral blood
Baseline to 12 weeks

Other Outcome Measures

Outcome Measure
Time Frame
The effect of liraglutide on levels of infiltrating dermal T cells and cytokines in psoriatic skin plaques from patients with psoriatic arthritis receiving liraglutide therapy for 12 weeks compared to those receiving placebo
Time Frame: Baseline to 12 weeks
Baseline to 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Collaborators

Novo Nordisk A/S

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2015

Primary Completion (Actual)

October 1, 2016

Study Completion (Actual)

October 1, 2016

Study Registration Dates

First Submitted

May 27, 2015

First Submitted That Met QC Criteria

June 11, 2015

First Posted (Estimate)

June 16, 2015

Study Record Updates

Last Update Posted (Actual)

July 17, 2017

Last Update Submitted That Met QC Criteria

July 14, 2017

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • U1111-1150-8501

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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