The Effect of Spironolactone on Pain in Older People With Osteoarthritis (SPIR-OA)

October 11, 2019 updated by: University of Dundee

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

86

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Fife
      • Kirkcaldy, Fife, United Kingdom, KY2 5AH
        • NHS Fife
    • Tayside
      • Dundee, Tayside, United Kingdom, DD1 9SY
        • NHS Tayside

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

70 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Matched Placebo
Drug: spironolactone
spironolactone 25mg daily for 12 weeks
Other Names:
  • Aldactone
Active Comparator: spironolactone
25mg spironolactone daily
Drug: spironolactone
spironolactone 25mg daily for 12 weeks
Other Names:
  • Aldactone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Between group difference in change in WOMAC pain subscale (5 items)
Time Frame: 12 weeks
12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Between group difference in change in WOMAC stiffness subscale.
Time Frame: 12 weeks
12 weeks

Other Outcome Measures

Outcome Measure
Time Frame
Between group difference in change in WOMAC physical function subscales.
Time Frame: 12 weeks
12 weeks
Between group difference in change in health-related quality of life measured by EQ-5D questionnaire.
Time Frame: 12 weeks
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Dundee

Collaborators

Arthritis Research UK

Investigators

  • Study Director: Marion ET McMurdo, MBChB, MD, University of Dundee
  • Principal Investigator: Miles Witham, BM BCh, MRCP, University of Dundee
  • Principal Investigator: Vera Cvoro, Mb CHB, MRCP, NHS Fife

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

May 1, 2015

Study Registration Dates

First Submitted

January 24, 2014

First Submitted That Met QC Criteria

January 27, 2014

First Posted (Estimate)

January 28, 2014

Study Record Updates

Last Update Posted (Actual)

October 14, 2019

Last Update Submitted That Met QC Criteria

October 11, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13/WS/0232
  • 2013-002638-19 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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