Clinical Trial: Timed Release Tablet Prednisone in Polymyalgia Rheumatica

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Circadian Variation in Cytokines and the Effect of Timed Release Tablet Prednisone in Polymyalgia Rheumatica

Brief Summary:

Polymyalgia Rheumatica (PMR) is a disease that usually affects older people. Patients complain of stiffness and pain around the shoulders and hips. The stiffness is more severe in the morning. The joints are not affected by this disease.

Research in Rheumatoid Arthritis (RA), which is also much worse in the mornings, has shown that IL−6 (a chemical messenger) peaks in the morning with very low levels in the evening. This may explain why stiffness is most severe in the morning. The investigators have recently shown that timed release tablet (TRT) prednisone reduced morning IL−6 levels close to normal in RA patients.

In PMR, IL−6 levels are high. Given that both RA and PMR have the same variation of symptoms (worse in the morning); it's likely that PMR patients have the same variation in IL−6 levels. In a pilot study of 4 patients conducted within our department, IL−6 levels did, indeed, show a pattern similar to that found in RA patients, but the number of patients is small and the results need to be confirmed.

PMR is treated with moderate doses of glucocorticoid for about 2 years. While generally abolishing symptoms, these doses are very likely to cause adverse effects such as high blood pressure, weight gain and diabetes. These side effects are much less frequent when lower doses are used but these are not sufficient to control PMR using traditional dosing regimes.

Therefore, the investigators wish to investigate whether TRT prednisone in PMR will reduce IL−6 and morning symptoms similar to those in RA. The investigators think that it will do so, and will achieve symptomatic relief at a lower dose. If this is the case, then treating patients with lower doses may mean reduced risk of gluco

Detailed Summary:

The volunteers will stay overnight in the Rheumatology Centre; 24-hour Research Facility on two occasions (Night A and Night B) 12-16 days apart. This slight flexibility will allow some leeway in arranging residency nights. In general the investigators will aim for 14 days. After Night A, each volunteer will be randomized (in pre-prepared sealed envelopes) to take one tablet morning or evening. Half the patients will take active standard release prednisolone in the morning. The other half will receive active TRT Prednisone 7mg to be taken each evening at 22:00 until the day after Night B. All study medication will then be discontinued and standard therapy (prednisolone 15mg each morning) commenced. Patients will be reviewed after 2 weeks to ensure expected clinical response and to measure IL-6 and other cytokines in the blood sample that is also needed to check the acute phase response.

On Night A and Night B, volunteers will attend the Rheumatology Centre at 15:00.

First, standard assessment tools will be used by the research doctor to assess the state of the patient's condition.

These assessments will be:

  • Morning stiffness (minutes)
  • Pain (visual analogue scale)
  • Patient's opinion of condition
  • Clinician's opinion of condition
  • Health Assessment Questionnaire
  • BRAF-MDQ fatigue scale and the Hospital Anxiety and Depression Scale.

An intravenous (IV) cannula will be inserted into the elbow area. At least one hour after the IV cannula is placed, but usually at 16:30, a bl
Sponsor: University Hospitals Bristol NHS Foundation Trust

Current Primary Outcome: Peak serum IL-6 concentration [ Time Frame: 24 hours ]

As measured from (approximately) hourly blood sampling over 24 hours


Original Primary Outcome: To show that the circadian variations in IL−6 and other cytokines in PMR can be altered by TRT Prednisone, and if this coincides with an improvement in symptoms. We will show that timing of treatment is important in the treatment of PMR. [ Time Frame: 18-24 months ]

Current Secondary Outcome:

  • Morning stiffness (minutes) [ Time Frame: 24 hours ]
    How long was your morning stiffness today?
  • Pain (severity) [ Time Frame: 24 hours ]
    100mm visual analogue scale. Question: How much pain have you had in the last 24 hours? Anchors: No pain; Severe pain.
  • Patient's opinion of condition [ Time Frame: Current ]
    100mm visual analogue sacale. Question: Considering all the ways your pain and/or stiffness affect(s) you, please mark on the line how well you are doing. Anchors: Very well; Very badly.
  • Clinician's opinion of disease activity. [ Time Frame: Current ]
    100mm visual analogue scale. Question: Clinician's opinion of disease activity. Anchors: None; Severe
  • PMR Disease Activity Score [ Time Frame: Current ]
    Numerical value of: CRP (mg/dl) + Patient's opinion of condition (mm) + Clinician's opinion of condition (mm) + morning stiffness (min x 0.1) + Elevation of upper limb (0-3 scale).
  • Serum cortisol [ Time Frame: 24 hours ]
    Measurement of circadian change in serum cortisol in (approximately) hourly blood samples
  • Disability (HAQ) [ Time Frame: Past week ]
    Health Assessment Questionnaire Disability Index
  • Fatigue (BRAF - MDQ) [ Time Frame: One week ]
    Bristol Rheumatoid Arthritis Fatigue Multi Dimensional Questionnaire


Original Secondary Outcome: We will advance our understanding of the pathogenesis (causes and mechanism) of PMR. [ Time Frame: 18-24 months ]

Information By: University Hospitals Bristol NHS Foundation Trust

Dates:
Date Received: February 2, 2009
Date Started: October 2009
Date Completion:
Last Updated: September 4, 2015
Last Verified: September 2015