Polymyalgia RheumaticaPhase 2/3NCT00836810
Timed Release Tablet Prednisone in Polymyalgia Rheumatica
A Phase 2/3 study testing Timed Release Tablet Prednisone and Prednisolone in people with Polymyalgia Rheumatica, run by University Hospitals Bristol and Weston NHS Foundation Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Polymyalgia Rheumatica
- What is being tested?
- Timed Release Tablet Prednisone and Prednisolone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2009to Mar 2011
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospitals Bristol NHS Trust
Bristol, Avon, BS2 8HW
About this study
Official title: Circadian Variation in Cytokines and the Effect of Timed Release Tablet Prednisone in Polymyalgia Rheumatica
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.
Read more
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.
Read the 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 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 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.
The investigators 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.
- Conditions
- Polymyalgia Rheumatica
- Being tested
- Timed Release Tablet Prednisone, Prednisolone
- Keywords
- Circadian variations of cytokines in PMR, effect of TRT Prednisone in cytokines
- Medical subject headings
- Polymyalgia Rheumatica
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Timed Release Tablet PrednisoneDrug
Also called Lodotra
Dose: 7mg, taken at 10pm every night for 2 weeks in the form of oral tablets.
PrednisoloneDrug
Dose: 7mg, taken in the morning for 2 weeks in the form of oral tablets.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Timed Release Tablet Prednisone |
| Standard Prednisolone | Active comparator | 12 patients will be taking morning Prednisolone at a dose of 7mg over 2 weeks. Receives: Drug: Prednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 24 hour measurements 2 weeks apart
Secondary outcomes (4)
Percentage Change in Morning Stiffness
How long was your morning stiffness today? Pre-treatment (Night A) value minus post-treatment (Night B) value divided by pre-treatment value.
Measured: 2 weeks
Pain (Severity)
100mm visual analogue scale. Question: How much pain have you had in the last 24 hours? Anchors: No pain; Severe pain. Min score 0, Max score 100. Higher value is worse outcome.
Measured: 24 hour period after 2 weeks of treatment
Patient's Opinion of Condition
100mm visual analogue scale. 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. Min 0 Max 100 (poor outcome).
Measured: Current value at baseline and after 2 weeks treatment
Clinician's Opinion of Disease Activity.
100mm visual analogue scale. Question: Clinician's opinion of disease activity. Anchors: None; Severe Min 0 Max 100 (worse)
Measured: Current at baseline and after 2 weeks treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2009 (estimated)
- Study startOct 2009
- Primary completionNov 2010
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Polymyalgia RheumaticaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Bristol and Weston NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John R Kirwan, MBBS,MD,FRCP, Principal investigator, University Hospitals Bristol and Weston NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00836810
- Sponsor's protocol ID
- ME/2008/3031
- Status last verified
- Aug 2022
- First submitted
- 2 Feb 2009
- Last updated
- 13 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circadian Variation in Cytokines and the Effect of Timed Release Tablet Prednisone in Polymyalgia Rheumatica
- ClinicalTrials.gov ID
- NCT00836810
- Acronym / sponsor ID
- ME/2008/3031
- Conditions
- Polymyalgia Rheumatica
- Keywords
- Circadian variations of cytokines in PMR, effect of TRT Prednisone in cytokines
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Hospitals Bristol and Weston NHS Foundation TrustUniversity, hospital or other
- Study start
- Oct 2009
- Primary completion
- Nov 2010 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 4 Feb 2009 (estimated)
- Results
- Posted 5 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 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 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.
The investigators 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Timed Release Tablet Prednisone | Experimental | Drug: Timed Release Tablet Prednisone12 patients will be taking the intervention night time timed release tablet (TRT) prednisone at a dose of 7mg a day over 2 weeks. |
| Standard Prednisolone | Active comparator | Drug: Prednisolone12 patients will be taking morning Prednisolone at a dose of 7mg over 2 weeks. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Diagnosis of PMR by standard criteria. The Bird criteria will be used. 3 or more features are required to make the diagnosis.
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Timed Release Tablet PrednisoneAlso: LodotraDose: 7mg, taken at 10pm every night for 2 weeks in the form of oral tablets. | Drug | Timed Release Tablet Prednisone |
| PrednisoloneDose: 7mg, taken in the morning for 2 weeks in the form of oral tablets. | Drug | Standard Prednisolone |
Primary outcome
Change in Peak Serum IL-6 Concentration
Time frame: 24 hours
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.
Change in Area Under the Curve (AUC) of Plasma IL-6
Time frame: 24 hour measurements 2 weeks apart
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).
4 secondary outcomes
Percentage Change in Morning Stiffness
Time frame: 2 weeks
Pain (Severity)
Time frame: 24 hour period after 2 weeks of treatment
Patient's Opinion of Condition
Time frame: Current value at baseline and after 2 weeks treatment
Clinician's Opinion of Disease Activity.
Time frame: Current at baseline and after 2 weeks treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John R Kirwan, MBBS,MD,FRCP principal investigator
University Hospitals Bristol and Weston NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Timed Release Tablet Prednisone and Prednisolone in people with Polymyalgia Rheumatica, run by University Hospitals Bristol and Weston NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Peak Serum IL-6 Concentration (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2022.