PLAQUE: Psoriatic Arthritis Treated With Liraglutide Therapy: a QUality of Life and Efficacy Study
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| 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:
|
| 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
|
Outcome Measures
Primary Outcome Measures
- 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 [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).
Secondary Outcome Measures
- 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 [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 [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 [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 [Baseline to 12 weeks]
Cardiovascular disease risk factors (Systolic blood pressure, cholesterol profiles, CRP, body weight, waist circumference)
- The effect(s) of liraglutide on the enumeration of circulating T-cell subpopulations, and on activation of circulating T-cell subpopulations [Baseline to 12 weeks]
Multi-parameter phospho flow cytometry analysis of T-cell differentiation and activation of peripheral blood
Other Outcome Measures
- 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 [Baseline to 12 weeks]
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Toronto Western Hospital, The Centre for Prognosis Studies in the Rheumatic Diseases (CPSRD), University of Toronto | Toronto | Ontario | Canada | M5T 2S8 |
Sponsors and Collaborators
- University Health Network, Toronto
- Novo Nordisk A/S
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- U1111-1150-8501