The Effect of Spironolactone on Pain in Older People With Osteoarthritis
Information source: University of Dundee
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Osteoarthritis, Knee
Intervention: spironolactone (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: University of Dundee Official(s) and/or principal investigator(s): Marion ET McMurdo, MBChB, MD, Study Director, Affiliation: University of Dundee Miles Witham, BM BCh, MRCP, Principal Investigator, Affiliation: University of Dundee Vera Cvoro, Mb CHB, MRCP, Principal Investigator, Affiliation: NHS Fife
Overall contact: Roberta DR Littleford, PhD, Phone: +44 1382 383242, Email: r.littleford@dundee.ac.uk
Summary
This pilot study will obtain preliminary evidence on which to base sample size calculations
for a future trial of whether spironolactone (an aldosterone blocker) reduces knee pain in
older people with symptomatic OA knee when given in addition to usual analgesia. Aldosterone
is known to be pro-inflammatory, and spironolactone suppresses cytokine production in
chronic arthritis. This application builds on previous work by the applicants showing that
spironolactone significantly improved quality of life (particularly pain) in frail older
people. The investigators will recruit 86 people (aged 70 years or over) with well-defined
OA knee to 25mg spironolactone daily or to matching placebo for 12 weeks. The primary
outcome is the between group difference in change in WOMAC pain sub-score at 12 weeks.
Secondary outcomes are the WOMAC stiffness and physical function subscales and health
related quality of life (EQ-5D). Morning cortisol levels will be measured to assess the
effect of mineralocorticoid receptor blockade on glucocorticoid levels, which may mediate
the anti-inflammatory effect of spironolactone; and urinary CTX-II, and serum matrix
metalloproteinase-3 (MMP-3) will be measured as biomarkers as both are sensitive to the
effects of pharmacological interventions for osteoarthritis.
Clinical Details
Official title: A Randomised Placebo Controlled Trial. The Effect of Spironolactone on Pain in Older People With Osteoarthritis
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Between group difference in change in WOMAC pain subscale (5 items)
Secondary outcome: Between group difference in change in WOMAC stiffness subscale.
Eligibility
Minimum age: 70 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Participant is willing and able to give informed consent
2. Community dwelling
3. Aged 70 years and over
4. Symptomatic idiopathic OA knee according to American College of Rheumatology clinical
and radiographic criteria (ie Knee pain - with or without crepitus and presence of
osteophytes on x ray)
5. To avoid floor effects, participants will require to have moderate (or more severe)
pain at screening in at least 2 out of 5 WOMAC pain score items
6. To have been in receipt (prescription or/and over the counter) of one or more
analgesic agents at a therapeutic dose for at least 2 months
7. Willing to have knee x-ray if one has not been taken in preceding 12 months
Exclusion Criteria:
1. Clinical diagnosis of symptomatic heart failure
2. History of inflammatory arthritis
3. Already taking spironolactone
4. Previous intolerance to spironolactone
5. Known allergies to spironolactone or lactose
6. Objection to taking capsules made from animal sourced gelatine
7. Taking oral NSAIDs (because of the increased risk of renal impairment when combined
with spironolactone)
8. Taking ACE inhibitors or ARBs (angiotensin II receptor antagonists). ARBs have many
properties similar to those of ACE inhibitors. Both will be exclusion because of the
increased risk of acute kidney injury and hyperkalaemia, and because our previous
study also excluded those on ACE inhibitors (and ARBs) and treatment was safe and
well tolerated.
9. Supine hypotension (supine systolic blood pressure <100mmHg at screening)
10. Significant chronic kidney disease (eGFR<40ml/min)
11. Serum sodium<130mmol/l
12. Serum potassium>5. 0mmol/l
13. Symptomatic orthostatic hypotension (measured at screening)
14. Nursing home resident
15. Wheelchair bound
16. Participating in another clinical trial (other than observational trials and
registries) concurrently or within 30 days prior to screening for entry into this
study
17. Known contraindication to spironolactone therapy
18. Participant who is terminally ill, defined as less than 3 months expected survival
Locations and Contacts
Roberta DR Littleford, PhD, Phone: +44 1382 383242, Email: r.littleford@dundee.ac.uk
NHS Fife, Kirkcaldy, Fife KY2 5AH, United Kingdom; Not yet recruiting Vera Cvoro, MbChB, MRCP, Principal Investigator
NHS Tayside, Dundee, Tayside DD1 9SY, United Kingdom; Recruiting Miles Witham, BM BCh, MRCP, Principal Investigator
Additional Information
Starting date: November 2013
Last updated: January 28, 2014
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