Clinical trial NCT02472717: Psoriatic Arthritis Treated With Liraglutide Therapy: a QUality of Life and Efficacy Study
Official title: Clinical Evaluation of Psoriatic Arthritis Treated With Liraglutide. The PLAQUE Study: Psoriatic Arthritis Treated With Liraglutide Therapy: a QUality of Life and Efficacy Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Psoriatic Arthritis
Psoriasis
Impaired Glucose Tolerance
Type 2 Diabetes
Keywords: liraglutide, GLP-1 receptor agonists
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2015-06-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline to 12 weeks, liraglutide compared to placebo
Secondary outcomes:
measure: 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
timeFrame: Baseline to 12 weeks
measure: 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
timeFrame: Baseline to 12 weeks
measure: 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
timeFrame: Baseline to 12 weeks
measure: 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
timeFrame: Baseline to 12 weeks
measure: The effect(s) of liraglutide on the enumeration of circulating T-cell subpopulations, and on activation of circulating T-cell subpopulations
timeFrame: Baseline to 12 weeks
Other outcomes:
measure: 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
timeFrame: Baseline to 12 weeks
Locations:
city: Toronto
country: Canada
facility: Toronto Western Hospital, The Centre for Prognosis Studies in the Rheumatic Diseases (CPSRD), University of Toronto
state: Ontario
Study officials:
References: