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Sarcoidosis is an inflammatory condition affecting many different parts of the body but most commonly the lungs. It is not known what causes sarcoidosis. In some patients no treatment is needed but in other patients long term treatment may be required.
One of the main medications used to manage this condition is corticosteroids. This medication has been shown to be very effective at reducing inflammation in this condition and many patients often remain on it for months to years.
Unfortunately, there are many negative long-term side effects of corticosteroid use. This includes an increased risk of developing diabetes, reduced bone density, weight gain, high blood pressure and low muscle mass. Currently there are no guidelines for how steroids should be weaned in patients who have stable sarcoidosis.
The investigators aim to undertake a study at the Royal Brompton Hospital which will be assessing two different steroid tapering regimens which will be allocated to participants in a randomised manner. This will be the first study to directly evaluate different steroid weaning regimens in sarcoidosis patients.
The main aim of this study is to determine how many participants can reduce their prednisolone dose to less than 50% from their baseline dose. Additionally, the investigators will be recording how many participants require an increase in dose or an additional medication whilst on the prednisolone weaning regimen. The investigators will also see the tolerability of steroid withdrawal and assess for any symptoms of steroid withdrawal. In a small subset of participants the investigators will assess for any changes in body composition and muscle strength using bioelectrical impedance analysis and isometric muscle testing.
This study will be assessing prednisolone tapering in patients with sarcoidosis. The investigators will be recruiting patients with stable sarcoidosis who are currently on a prednisolone dose between 5mg-10mg/day. The study aims to determine if participants are able to reduce their prednisolone dose to at least 50% of their initial baseline dose when entering the trial.
The two tapering regimens are as follows:
Standard taper: If prednisolone > 5mg/day then reduce by 2.5mg/day (round to nearest feasible dose) every 4 weeks until reaching 5mg/day. From 5 mg/day to reduce by 1mg/day every 6 weeks until 3mg/day. At 3 mg/day: measure serum cortisol. If cortisol > 25nmol/L, then continue with Meeran prednisolone taper protocol which is reducing by 1mg every 7 days.
Fast taper: If prednisolone > 5mg/day then reduce by 2.5mg/day (round to nearest feasible dose) every 4 weeks until reaching 5mg/day. From 5 mg/day: reduce by 1 mg every 2 weeks until 3 mg /day. At 3 mg/day then measure serum cortisol: If cortisol > 25nmol/L, continue taper by 1 mg every 2 weeks. In this fast taper participants will be contacted over the phone every 2 weeks to provide support with the tapering regimen.
Participants who meet both the inclusion and exclusion criteria will be screened. Informed consent will then be performed and the following demographic and clinical characteristics will be collected (age, sex, smoking history, ethnicity, co-morbidities, medications and baseline lung function data (FEV1% predicted, FVC% predicted, DLCO% predicted). If lung function testing has not been performed in the previous 6 months this will be arranged. A dedicated lung function slot has been allocated once every week to facilitate this as agreed upon with the head of the lung function department.
Participants will then be randomised to either the standard or the fast prednisolone tapering regimen by computer-generated sequence using random block design with stratification by background steroid sparing agents.
After randomisation, a baseline visit will occur this will be an in person visit at the Royal Brompton Hospital. At the baseline visit the following questionnaires will be performed kings sarcoidosis questionnaire (KSQ), fatigue assessment score (FAS), patient global assessment (PGA) and addison's disease (AD) quality of life questionnaire (AddiQoL).
In a subset of participants (30 patients, 15 per arm) further testing on body composition will be performed and includes bioelectrical impedance analysis, 5 times sit to stand testing and isometric quadriceps testing (these tests will all be performed at the Royal Brompton Hospital).
The next visit which will be performed as a phone visit will be once participants reach a prednisolone dose of 5mg/day (this visit will not occur in any participants who have a starting baseline prednisolone dose of 5mg). At this visit the following questionnaires will be performed kings sarcoidosis questionnaire (KSQ), fatigue assessment score (FAS), patient global assessment (PGA) and addison's disease (AD) quality of life questionnaire (AddiQoL).
The next visit will be performed as a phone visit once participants reach a prednisolone dose of 3mg/day. At this visit the following questionnaires will be performed kings sarcoidosis questionnaire (KSQ), fatigue assessment score (FAS), patient global assessment (PGA) and addison's disease (AD) quality of life questionnaire (AddiQoL).
Additionally, all participants 2 weeks after reaching prednisolone 3mg/day will have a serum cortisol measurement taken. This test is performed as part of routine clinical practice and will be performed at the pathology department at the Royal Brompton Hospital.
The final visit will be performed as a phone visit 6 weeks after participants have completed the tapering regimen or have reached the lowest achievable prednisolone dose. At this final visit the following questionnaires will be performed; kings sarcoidosis questionnaire (KSQ), fatigue assessment score (FAS), patient global assessment (PGA) and addison's disease (AD) quality of life questionnaire (AddiQoL).
Additionally in the same subset of patients who underwent body composition assessment at the baseline visit bioelectrical impedance analysis, 5 times sit to stand testing and isometric quadriceps testing (these tests will all be performed at the Royal Brompton Hospital).
After 12 months following randomisation, participants medical records will be reviewed to determine current prednisolone dose. No patient contact is required at this stage.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard prednisolone taper | Active Comparator | If initial dose of prednisolone > 5mg/day then dose will be reduced by 2.5mg/day (round to nearest feasible dose) every 4 weeks until reaching 5mg/day. From 5mg/day to reduce by 1mg/day every 6 weeks until 3mg/day. At 3mg/day a serum cortisol will be measured after 2 weeks. If cortisol > 25nmol/L, then continue with the Meeran prednisolone taper protocol which is reducing by 1mg every 7 days. |
|
| Fast prednisolone taper | Active Comparator | If initial prednisolone dose > 5mg/day then reduce by 2.5mg/day (round to nearest feasible dose) every 4 weeks until reaching 5mg/day. From 5mg/day to reduce by 1mg every 2 weeks until 3mg/day. At 3mg/day then measure serum cortisol after 2 weeks. If cortisol > 25nmol/L then continue to taper by 1mg every 2 weeks. In this arm, patients will contacted over the phone every 2 weeks to provide support with the tapering regimen. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standard prednisolone taper | Drug | If initial dose of prednisolone > 5mg/day then dose will be reduced by 2.5mg/day (round to nearest feasible dose) every 4 weeks until reaching 5mg/day. From 5mg/day to reduce by 1mg/day every 6 weeks until 3mg/day. At 3mg/day a serum cortisol will be measured after 2 weeks. If cortisol > 25nmol/L, then continue with the Meeran prednisolone taper protocol which is reducing by 1mg every 7 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients achieving a prednisolone dose < 50% of baseline dose | To evaluate the proportion of patients achieving a prednisolone dose ≤50% of baseline utilising two tapering regimens (standard vs. fast) while maintaining clinical stability | From enrolment to 6 weeks after complete steroid wean or lowest prednisolone dose achieved |
| Measure | Description | Time Frame |
|---|---|---|
| The need for initiation or escalation of non-steroidal immunosuppressive therapy | To evaluate the proportion of patients achieving a prednisolone dose ≤50% of baseline without the need for initiation or escalation of non-steroidal immunosuppressive therapy | Enrolment to 6 weeks after either complete steroid wean or lowest achieved prednisolone dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Vasileios Kouranos | Contact | +44(0) 207 352 8121 | 84405 | vasileios.kouranos@nhs.net |
| Jessica Raja | Contact | jessica.raja2@nhs.net |
| Name | Affiliation | Role |
|---|---|---|
| Vasileios Kouranos | Interstitial Lung Disease Department, Royal Brompton Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Brompton Hospital | Recruiting | London | SW36NP | United Kingdom |
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| ID | Term |
|---|---|
| D012507 | Sarcoidosis |
| ID | Term |
|---|---|
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006968 | Hypersensitivity, Delayed |
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| Fast prednisolone taper | Drug | If initial prednisolone dose > 5mg/day then reduce by 2.5mg/day (round to nearest feasible dose) every 4 weeks until reaching 5mg/day. From 5mg/day to reduce by 1mg every 2 weeks until 3mg/day. At 3mg/day then measure serum cortisol after 2 weeks. If cortisol > 25nmol/L then continue to taper by 1mg every 2 weeks. In this arm, patients will contacted over the phone every 2 weeks to provide support with the tapering regimen. |
|
| Number and length of interruptions to prednisolone taper | Measurement of the number and the length of any interruptions to the prednisolone taper | Enrolment until 6 weeks following complete steroid wean or lowest achieved prednisolone dose |
| Evaluation of changes in quality of life | Using the King's sarcoidosis questionnaire (KSQ) to determine any changes in quality of life with prednisolone tapering This questionnaire will be performed at:
There are 5 domains (general health status, lung, skin, eyes and medications) each domain is scored between a range between 0-100. 0 indicates the lowest or worst health status and 100 indicates the best health/highest quality of life. | See in description as insufficient space for the detail above to be entered in this section |
| Proportion of patients with cortisol levels < 25nmol/L at prednisolone dose 3mg/day | 2 weeks following reaching prednisolone dose of 3mg/day, morning blood cortisol level will be taken | This will be performed 2 weeks after reaching prednisolone dose of 3mg/day |
| Assess for symptoms of steroid withdrawal, safety and tolerability with prednisolone weaning | Using Addison's Disease (AD) quality of life questionnaire (AddiQoL) to determine if any symptoms of steroid withdrawal This questionnaire will be performed at:
The final total score is calculated as the algebraic sum of all item scores, with a maximum possible score of 120 points, a higher total score indicates a better overall quality of life (there are no specific cut-off scores). | See in description as insufficient space for the detail above to be entered in this section |
| Evaluation of prednisolone dose | Prednisolone dose will be recorded at:
| See in description as insufficient space for the detail above to be entered in this section |
| Changes in body composition measured with bioimpedance analysis (BIA) | In a subset of 30 patients (15 in each arm) we will performing bioimpedance analysis to determine any changes in body composition. We will recording phase angle (PhA) which is measured in units ° (degrees) and is a calculated value provided by the bioimpedance machine. | BIA will be performed at the baseline visit and final visit (6 weeks following complete steroid wean or lowest achieved steroid dose). |
| Change in body composition using isometric quadriceps testing strength | In a subset of 30 patients (15 in each arm) we will be performing isometric quadriceps testing. | This will be performed at baseline and final visit (6 weeks following complete prednisolone wean or lowest achieved prednisolone dose). |
| Changes in body composition using 5 times sit to stand test (5STS) | This test will be performed in a subset of 30 patients (15 in each arm). The 5STS is a functional test assessing quadricep strength. | 5STS will be performed at baseline and final visit (6 weeks following complete steroid wean or lowest achieved steroid dose). |
| Evaluation of changes in quality of life and fatigue | Using the fatigue assessment scale (FAS) to determine any changes in quality of life with prednisolone tapering This questionnaire will be performed at:
Fatigue assessment scale is score range 10-50. Less than 22 indicates normal levels of fatigue, 22-34 indicates mild to moderate fatigue, greater than 35 indicates severe fatigue | See in description as insufficient space for the detail above to be entered in this section |
| Changes in body composition measured with bioimpedance analysis (BIA) | In a subset of 30 patients (15 in each arm) we will performing bioimpedance analysis to determine any changes in body composition. We will recording skeletal muscle mass (SMM) which is measured in kg. | This testing will be performed at the baseline visit and final visit (6 weeks following complete steroid wean or lowest achieved steroid dose). |
| Changes in body composition measured with bioimpedance analysis (BIA) | In a subset of 30 patients (15 in each arm) we will performing bioimpedance analysis to determine any changes in body composition. We will recording phase fat free muscle index (FFMI) which is calculated by the bioimpedance machine by the measurement of fat free mass (measured in kg) divided by height in m^2. (FFM(kg)/m^2 = fat free mass index (FFMI). | This measurement will be performed at the baseline visit and final visit (6 weeks following complete steroid wean or lowest achieved steroid dose). |
| Changes in body composition measured with bioimpedance analysis (BIA) | In a subset of 30 patients (15 in each arm) we will performing bioimpedance analysis to determine any changes in body composition. We will recording appendicular skeletal muscle mass (ASMM) which is measured in kg. | This measurement will be performed at the baseline visit and final visit (6 weeks following complete steroid wean or lowest achieved steroid dose). |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |