Timed Release Tablet Prednisone in Polymyalgia Rheumatica

NCT00836810 | Completed Phase 2 Results

• 1 other identifier: ME/2008/3031
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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. 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.

Conditions

Polymyalgia Rheumatica

Keywords

Circadian variations of cytokines in PMR; effect of TRT Prednisone in cytokines

Outcome Measures

Primary Outcomes (2)

• Change in Peak Serum IL-6 Concentration

  Pre-treatment (Night A) peak minus post-treatment (Night B) peak. Peaks defined as the highest value for each patient from measures at 0, 1.5, 3, 4.5, 5.5, 6.5, 7.5, 8.5, 9.5, 10.5, 11.5, 12.5, 13.5, 14.5, 15.5, 17, 19, 20.5, 22, and 24 hours after 16.30 on day before treatment (Night A) and last day of treatment (Night B) and the peak identified for each one.

  24 hours

• Change in Area Under the Curve (AUC) of Plasma IL-6

  Pre-treatment (Night A) AUC minus post-treatment (Night B) AUC. AUC calculated from measures at 0, 1.5, 3, 4.5, 5.5, 6.5, 7.5, 8.5, 9.5, 10.5, 11.5, 12.5, 13.5, 14.5, 15.5, 17, 19, 20.5, 22, and 24 hours after 16.30 on day before treatment (Night A) and last day of treatment (Night B).

  24 hour measurements 2 weeks apart

Secondary Outcomes (4)

• Percentage Change in Morning Stiffness

  2 weeks

• Pain (Severity)

  24 hour period after 2 weeks of treatment

• Patient's Opinion of Condition

  Current value at baseline and after 2 weeks treatment

• Clinician's Opinion of Disease Activity.

  Current at baseline and after 2 weeks treatment

Study Arms (2)

Timed Release Tablet Prednisone

EXPERIMENTAL

12 patients will be taking the intervention night time timed release tablet (TRT) prednisone at a dose of 7mg a day over 2 weeks.

Drug: Timed Release Tablet Prednisone

Standard Prednisolone

ACTIVE COMPARATOR

12 patients will be taking morning Prednisolone at a dose of 7mg over 2 weeks.

Drug: Prednisolone

Interventions

Timed Release Tablet Prednisone DRUG

Dose: 7mg, taken at 10pm every night for 2 weeks in the form of oral tablets.

Also known as: Lodotra

Timed Release Tablet Prednisone

Prednisolone DRUG

Dose: 7mg, taken in the morning for 2 weeks in the form of oral tablets.

Standard Prednisolone

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \<2/52
• Initial ESR \>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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospitals Bristol and Weston NHS Foundation Trust: lead

Study Sites (1)

University Hospitals Bristol NHS Trust

Bristol, Avon, BS2 8HW, United Kingdom

Location

MeSH Terms

Conditions

Polymyalgia Rheumatica

Interventions

Prednisolone

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Small number of patients not blind to study treatment which may have influenced reports of morning stiffness.

Results Point of Contact

• Title: Professor John Kirwan
• Organization: University of Bristol

John.Kirwan@Bristol.ac.uk

+44 117 342 2904

Study Officials

• John R Kirwan, MBBS,MD,FRCP

  University Hospitals Bristol and Weston NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2009
• First Posted: February 4, 2009
• Study Start: October 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: March 1, 2011
• Last Updated: September 13, 2022
• Results First Posted: February 5, 2018

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)