Pentosan Polysulphate (PPS) for Dyslipidaemia in Knee Osteoarthritis

Phase 1

Completed

• Conditions: Osteoarthritis; Dyslipidaemia; Musculoskeletal - Osteoarthritis

• Registration Number: ACTRN12619000047190
• Lead Sponsor: niversity of Sydney

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-01-14
• Study Completion: 2020-04-20
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

A.Male or female patients minimum of 45 years or more;
B.Are able to give written informed consent and to participate fully in the interventions and follow-up procedures including travel to the Royal North Shore Hospital;
C.Have history of primary hypercholesterolemia and total fasting cholesterol above 5.0mmol/L at screening;
D.Have any symptoms associated with OA of the knee for at least 6 months prior to screening visit and confirmation of OA based on the clinical and radiological criteria of American College of Rheumatology Criteria for OA (Altman et al, 1986) of the knee prior or at screening.
E.Kellgren-Lawrence (K-L) Grade 2 or 3 in the index knee based on knee radiograph performed at screening or within six months of the screening visit;
F.Have Index knee pain on most days over the last month.
G.Knee Pain Severity Scale above 4 using an 11-point (0-10) numerical severity scale where 0 is no pain at all and 10 is worst possible pain in the last 48 hours at baseline visit;
(If both knees are affected by OA then the most symptomatic knee will be considered the index knee. If both knees are equally affected, the index knee will be determined by the Investigator.)
H.BMI<40 kg/m2 at screening visit;
I.Agree to maintain their usual activity level and diet throughout the study;
J.Female of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation;

Exclusion Criteria

A.Documented history of Fibromyalgia, Reiter’s syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease;
B.Known hypersensitivity to Pentosan Polysulfate or related compounds (e.g. heparin);
C.Any unstable concurrent clinically significant acute, chronic medical conditions or abnormal laboratory findings that, in the judgment of the Investigator, would jeopardise the safety of the patient, interfere with the objectives of the protocol, or affect the patients compliance with the study requirements, as determined by the investigator;
D.Contraindications for MRI including but not limited to pacemaker, metal sutures, presence of shrapnel, or claustrophobia;
E.Current or a recent history (within last 12 months) of bleeding (a gastric or duodenal ulcer or suspicion of GI tract bleeding) or menorrhagia;
F.Haemophilia ;
G.Planned / anticipated invasive procedure (or surgery) within 6 months;
H.Recent surgery;
I.Bilateral Knee replacement
J.Concurrent heparin or oral anti-coagulant therapy;
K.Concurrent therapy with lipid –modifying drugs for hypercholesterolemia;
L.Female patients who are pregnant, nursing or intend to get pregnant;
M. Use of prohibited pain medication( see below)
•Oral non-steroidal anti-inflammatory drugs (NSAIDs)
•Aspirin (>325 mg per day)
•Centrally-acting pain medications (e.g., pregabalin, gabapentin, duloxetine)
•Opioids (e.g. tramadol)
•Topical therapies (e.g., NSAIDs ) applied to the index knee
•Muscle relaxants (e.g. tetrazepam, diazepam)
N. Prohibited Concomitant Medications:
• Lipid-modifying drugs: statins ( e.g. atorvastatin, pravastatin and simvastatin) or ezetimibe (Ezetrol)
• Anticoagulants including heparin, warfarin, apixaban (Eliquis), dabigatran (Pradaxa) and rivaroxaban (Xarelto)
• Biological/ disease –modifying anti-rheumatic drugs for arthritis
• Steroid drugs for systematic use

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary outcome of interest is the change in serum triglycerides levels [Baseline, 16 weeks post baseline visit]

Secondary Outcome Measures

Name	Time	Method
Change from baseline in blood Cholesterol through serum assay<br>[ 6, 26 weeks post baseline visit];Changes from baseline in Full blood counts (FBC)[6,16,26 weeks post baseline visit];Changes from baseline in Prothrombin time (PT) through plasma assay[6,16,26 weeks post baseline visit];Composite changes from baseline in Self-reported outcomes of pain, stiffness and functional status measured using the Knee Osteoarthritis Outcome Score (KOOS) [6,16,26 weeks post baseline visit];Changes from Baseline in Severity Knee Pain Score [6,16,26 weeks post baseline visit];Composite Changes from baseline in Sub-chondral bone structure,density, vascularity by MRI[26 weeks post baseline visit];Changes from baseline in Activated Partial thromboplastin time (APTT) through plasma assay[6,16,26 weeks post baseline visit];Changes from baseline in D-Dimer through plasma assay[6,16,26 weeks post baseline visit]