The Effect of Spironolactone on Pain in Older People With Osteoarthritis

Osteoarthritis, Knee Clinical Trial

— SPIR-OA  

Official title:

A Randomised Placebo Controlled Trial. The Effect of Spironolactone on Pain in Older People With Osteoarthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02046668
• Other study ID #: 13/WS/0232
• Secondary ID: 2013-002638-19
• Status: Completed
• Phase: Phase 4
• Start date: November 2013
• Est. completion date: May 2015

Study information

• Verified date: October 2019
• Source: University of Dundee
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: May 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• spironolactone
spironolactone 25mg daily for 12 weeks

Locations

Country	Name	City	State
United Kingdom	NHS Tayside	Dundee	Tayside
United Kingdom	NHS Fife	Kirkcaldy	Fife

Sponsors (2)

Lead Sponsor	Collaborator
University of Dundee	Arthritis Research UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Between group difference in change in WOMAC physical function subscales.		12 weeks
Other	Between group difference in change in health-related quality of life measured by EQ-5D questionnaire.		12 weeks
Primary	Between group difference in change in WOMAC pain subscale (5 items)		12 weeks
Secondary	Between group difference in change in WOMAC stiffness subscale.		12 weeks

External Links

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