Full Text View
Tabular View
No Study Results Posted
Related Studies
Timed Release Tablet Prednisone in Polymyalgia Rheumatica
This study is currently recruiting participants.
Verified by University Hospitals Bristol NHS Trust, October 2009
First Received: February 2, 2009   Last Updated: October 2, 2009   History of Changes
Sponsor: University Hospitals Bristol NHS Trust
Information provided by: University Hospitals Bristol NHS Trust
ClinicalTrials.gov Identifier: NCT00836810
  Purpose

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 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.


Condition Intervention Phase
Polymyalgia Rheumatica
Drug: Timed Release Tablet Prednisone
Drug: Prednisolone
Phase II
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Efficacy Study
Official Title: Circadian Variation in Cytokines and the Effect of Timed Release Tablet Prednisone in Polymyalgia Rheumatica

Resource links provided by NLM:


Further study details as provided by University Hospitals Bristol NHS Trust:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • We will advance our understanding of the pathogenesis (causes and mechanism) of PMR. [ Time Frame: 18-24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: October 2009
Estimated Study Completion Date: February 2011
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
TRT Prednisone: Experimental
12 patients will be taking night time TRT prednisone at a dose of 7mg a day over 2 weeks.
Drug: Timed Release Tablet Prednisone
Dose: 7mg, taken at 10pm every night for 2 weeks in the form of oral tablets.
Standard Prednisolone: Active Comparator
12 patients will be taking morning Prednisolone at a dose of 7mg over 2 weeks.
Drug: Prednisolone
Dose: 7mg, taken in the morning for 2 weeks in the form of oral tablets.

Detailed Description:

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 we will aim for 14 days. After Night A, each volunteer will be randomised (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 blood sample (2ml) will be taken through the IV cannula and the cannula flushed. At 22:30 the main lights will be switched off and the volunteer encouraged to sleep. In total, 20 samples will be taken from the cannula over 24 hours.

We will calculate mean and standard deviation (or non-parametric analysis if the data are not normally distributed) for blood cytokines for each time point. These mean and standard deviations will be compared for pre- and post-TRT prednisone samples.

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 <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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00836810

Contacts
Contact: Samy Zakout, MBBCh, MRCP +44(0)1173422515 Samy.Zakout@Bristol.ac.uk
Contact: John Kirwan R Kirwan, MBBS,MD,FRCP +44(0)1173422904 John.Kirwan@Bristol.ac.uk

Locations
United Kingdom, Avon
University Hospitals Bristol NHS Trust Recruiting
Bristol, Avon, United Kingdom, BS2 8HW
Contact: Samy Zakout, MD     +44 117 342 2906     Samy.Zakout@bristol.ac.uk    
Contact: Dorcas Perry     +44 117 342 2906     mdxdp@Bristol.ac.uk    
Principal Investigator: John R Kirwan, MBBS,MD,FRCP            
Sponsors and Collaborators
University Hospitals Bristol NHS Trust
Investigators
Principal Investigator: John R Kirwan, MBBS,MD,FRCP University Hospitals Bristol NHS Trust
  More Information

No publications provided

Responsible Party: University Hospitals Bristol ( Prof. John R Kirwan )
Study ID Numbers: ME/2008/3031
Study First Received: February 2, 2009
Last Updated: October 2, 2009
ClinicalTrials.gov Identifier: NCT00836810     History of Changes
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University Hospitals Bristol NHS Trust:
Circadian variations of cytokines in PMR
effect of TRT Prednisone in cytokines

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Prednisone
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Vasculitis, Central Nervous System
Brain Diseases
Hormones
Cerebrovascular Disorders
Musculoskeletal Diseases
Therapeutic Uses
Connective Tissue Diseases
Cardiovascular Diseases
Arteritis
Autoimmune Diseases of the Nervous System
Skin Diseases, Vascular
Vasculitis
Autoimmune Diseases
Antineoplastic Agents, Hormonal
Skin Diseases
Immune System Diseases
Nervous System Diseases
Vascular Diseases
Central Nervous System Diseases
Rheumatic Diseases
Glucocorticoids
Pharmacologic Actions
Muscular Diseases
Giant Cell Arteritis
Polymyalgia Rheumatica

ClinicalTrials.gov processed this record on February 08, 2010