Hydroxychloroquine/Atorvastatin in the Treatment of Osteoarthritis (OA) of the Knee

NCT01645176 | Completed Phase 2 Results DMC

• 1 other identifier: 23784
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study of a combination therapy of hydroxychloroquine and atorvastatin is to learn about the effects in inflammation and pain in patients with Osteoarthritis of the knee. These medications are FDA approved and commercially available.

Conditions

Osteoarthritis of the Knee

Keywords

OA; Knee

Outcome Measures

Primary Outcomes (1)

• Change in Synovitis

  MRI readings performed independently by two musculoskeletal radiologists, using a semi-quantitative scoring system based on MRI assessment of knee OASynovitis scored using axial \& sagittal CE-MRI sequence, while effusion \& bone marrow lesions were scored using non-CE-MRI sequences of parent study. Synovitis defined as enhancing thickened synovium (\>2 mm) \& was evaluated at nine sites of joint-medial \& lateral parapatellar recess, suprapateller, infrapatellar, intercondylar, medial \& lateral perimeniscal, \& adjacent to anterior \& posterior cruciate ligaments (ACL/PCL) in all subjects. Synovial thickness was scored semi-quantitatively based on maximal thickness in any slice at each site as follows: grade 0 if \<2mm, grade 1 if 2-4 mm \& grade 2 if \>4mm. For assessment of whole knee synovitis scores of all sites were summed and categorized: 0-4 normal or equivocal synovitis; 5-8 mild synovitis; 9-12 moderate synovitis \& \>/= 13 severe synovitis.

  baseline and 16 weeks

Study Arms (1)

Hydroxychloroquine/Atorvastatin open label

EXPERIMENTAL

Drug: Hydroxychloroquine/Atorvastatin

Interventions

Hydroxychloroquine/Atorvastatin DRUG

Hydroxychloroquine 200-600 mg /day Atorvastatin 40 mg/day

Hydroxychloroquine/Atorvastatin open label

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ambulatory subjects with OA of the knee with symptoms for at least 6 months and pain on the majority of days in the last 30 days. Symptoms must include knee joint pain.
• Male or female adults age \>40 years with a body mass index \<35
• Radiographic evidence of at least one osteophyte in either knee on posteroanterior (PA) and lateral standing, flexed x-ray.
• A Kellegren-Lawrence score of 2-3, or KL score of 1 accompanied by a clinically apparent effusion in the index knee.
• A WOMAC pain score of \>8 on the index knee at screening visit.

You may not qualify if:

• A requirement for treatment with high potency opioids for pain relief.
• Unwilling to abstain from NSAIDs and/or other analgesic medications except acetaminophen (i.e., COX-2 inhibitors, tramadol) for 48 hours and acetaminophen for 24 hours prior to pain assessments during the study. Subjects taking low dose aspirin for cardiovascular health may remain on their stable dose throughout the study.
• On an unstable dose of NSAIDs or analgesics for at least 1 months prior to screening visit 1.
• Using a handicap assistance device (i.e., cane, walker) \>50% of the time.
• Undergoing new physical therapy or participating in a weight loss or exercise program that has not been stable for at least 3 months prior to screening visit 1 and will not remain stable during their participation in the study.
• Had a previous history of arthroscopic or open surgery to the index knee in the past 6 months or planned surgery during study follow up.
• Had joint replacement surgery in the index knee.
• Received corticosteroid, short acting hyaluronic acid, or other intraarticular injections of the index knee within 3 months of screening visit 1 and/or not willing to abstain from treatments for the duration of the study
• A history in the past 5-10 years of reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis, amyloidosis or fibromyalgia.
• Clinical signs and symptoms of active knee infection or radiographic evidence of crystal disease other than chondrocalcinosis (i.e. gout).
• A history of abnormal laboratory results \>2.5 x ULN indicative of any significant medical disease, which in the opinion of the investigator, would preclude the subjects participation in the study
• Any of the following abnormal laboratory results during screening:
• ALT and/or AST \>2.5x ULN
• Hemoglobin \<9 g/dL
• WBC \<3500 cells/mm3

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Hydroxychloroquine; Atorvastatin

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Mark C. Genovese
• Organization: Stanford University School of Medicine

genovese@stanford.edu

650-498-4528

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: May 31, 2012
• First Posted: July 20, 2012
• Study Start: May 1, 2012
• Primary Completion: April 1, 2016
• Study Completion: October 1, 2016
• Last Updated: July 13, 2018
• Results First Posted: May 8, 2017

Record last verified: 2018-07

Locations

US (1)