The Effect of Spironolactone on Pain in Older People With Osteoarthritis

NCT02046668 | Completed Phase 4 DMC

• 2 other identifiers: 13/WS/02322013-002638-19
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Osteoarthritis, Knee

Keywords

Osteoarthritis of knee

Outcome Measures

Primary Outcomes (1)

• Between group difference in change in WOMAC pain subscale (5 items)

  12 weeks

Secondary Outcomes (1)

• Between group difference in change in WOMAC stiffness subscale.

  12 weeks

Other Outcomes (2)

• Between group difference in change in WOMAC physical function subscales.

  12 weeks

• Between group difference in change in health-related quality of life measured by EQ-5D questionnaire.

  12 weeks

Study Arms (2)

spironolactone

ACTIVE COMPARATOR

25mg spironolactone daily

Drug: spironolactone

Placebo

PLACEBO COMPARATOR

Matched Placebo

Drug: spironolactone

Interventions

spironolactone DRUG

spironolactone 25mg daily for 12 weeks

Also known as: Aldactone

Placebo; spironolactone

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Participant is willing and able to give informed consent
• Community dwelling
• Aged 70 years and over
• 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)
• 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
• 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
• Willing to have knee x-ray if one has not been taken in preceding 12 months

You may not qualify if:

• Clinical diagnosis of symptomatic heart failure
• History of inflammatory arthritis
• Already taking spironolactone
• Previous intolerance to spironolactone
• Known allergies to spironolactone or lactose
• Objection to taking capsules made from animal sourced gelatine
• Taking oral NSAIDs (because of the increased risk of renal impairment when combined with spironolactone)
• Supine hypotension (supine systolic blood pressure \<100mmHg at screening)
• Significant chronic kidney disease (eGFR\<40ml/min)
• Serum sodium\<130mmol/l
• Serum potassium\>5.0mmol/l
• Symptomatic orthostatic hypotension (measured at screening)
• Nursing home resident
• Wheelchair bound
• Participating in another clinical trial (other than observational trials and registries) concurrently or within 30 days prior to screening for entry into this study

Sponsors & Collaborators

• University of Dundee: lead
• Arthritis Research UK: collaborator

Study Sites (2)

NHS Fife

Kirkcaldy, Fife, KY2 5AH, United Kingdom

Location

NHS Tayside

Dundee, Tayside, DD1 9SY, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Marion ET McMurdo, MBChB, MD

  University of Dundee

  STUDY DIRECTOR

• Miles Witham, BM BCh, MRCP

  University of Dundee

  PRINCIPAL INVESTIGATOR

• Vera Cvoro, Mb CHB, MRCP

  NHS Fife

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2014
• First Posted: January 28, 2014
• Study Start: November 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: May 1, 2015
• Last Updated: October 14, 2019

Record last verified: 2019-10

Locations

GB (2)