Phase 3
N=11
Timed Release Tablet Prednisone in Polymyalgia Rheumatica
Polymyalgia Rheumatica
Bottom Line
View on ClinicalTrials.gov: NCT00836810 ↗Enrolled (actual)
11
Serious AEs
0.0%
Results posted
Feb 2018
Primary outcome: Primary: Change in Peak Serum IL-6 Concentration — 11.5; 29.3 pg/ml — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Timed Release Tablet Prednisone (Drug); Prednisolone (Drug)
- Age
- Adult, Older Adult · 50+ yrs
- Sex
- All
- Sponsor
- University Hospitals Bristol and Weston NHS Foundation Trust
- Primary completion
- Nov 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Peak Serum IL-6 Concentration |
11.5; 29.3 | <0.001 sig |
| PRIMARY Change in Area Under the Curve (AUC) of Plasma IL-6 |
113.5; 97.9 | <0.001 sig |
| SECONDARY Percentage Change in Morning Stiffness |
75.0; 115.0 | 0.023 sig |
| SECONDARY Pain (Severity) |
26.5; 19.5 | 0.007 sig |
| SECONDARY Patient's Opinion of Condition |
17.8; 26.0 | 0.022 sig |
| SECONDARY Clinician's Opinion of Disease Activity. |
19.0; 20.3 | .003 sig |
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.
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 glucocorticoid induced side effects in the future.
Patients will be recruited through the outpatient clinics at the University Hospitals Bristol, NHS Foundation Trust, Rheumatology Centre. Each patient will give fully informed consent after being given details of the study and a patient information sheet. The research doctor will take the consent 2-5 days after this information has been provided and with the presence of a witness. The study will consist of the collection and analysis of sequential blood samples over a 24 hour period on 2 occasions 2 weeks apart, taking TRT prednisone 7 mg / standard release prednisolone 7 mg for the intervening period. The investigators will aim to recruit 12 patients in each arm. A single blood sample will be taken when the patient comes for a routine review 2 weeks later.
Eligibility Criteria
Inclusion Criteria
- Diagnosis of PMR by standard criteria. The Bird criteria will be used. 3 or more features are required to make the diagnosis.
- Bilateral shoulder pain/stiffness
- Duration of symptoms 40 mm/h
- Stiffness >1 h
- Age >65 years
- Depression and/or weight loss
- Bilateral upper arm tenderness
- Are over 50 but less than 85 years old.
- No or stable NSAID or analgesic therapy for at least 7 days.
- Currently active disease defined by a CRP at least 10mg/L, ESR at least 29mm in one hour or PV >1.72
Exclusion Criteria
- Currently on oral glucocorticoid treatment or taken within 2 months
- Parenteral glucocorticoid treatment with the last 2 months
- Pregnancy and lactation
- Inflammatory diseases such as inflammatory bowel disease, colitis, asthma
- Co-existent giant cell arteritis
- Other auto-immune diseases
- Cancer
- Infections, treatment with antibiotics within the past 6 weeks
- Significant renal disease (creatinine >150 μmol/L)
- Significant hepatic impairment
- Participation in a clinical trial within the past 30 days
- Working shift employee
- Jet lag
Data sourced from ClinicalTrials.gov (NCT00836810). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.