Sarcoidosis
Conditions
Keywords
corticosteroid tapering
Brief summary
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.
Detailed description
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.
Interventions
DRUGStandard prednisolone taper
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.
DRUGFast prednisolone taper
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.
Sponsors
Royal Brompton & Harefield NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed sarcoidosis by: (a) Histological diagnosis and/or (b) Multidisciplinary Team (MDT) diagnosis * Prednisolone 5-10mg/day for \> 6 months * Clinically stable disease for \> 6 months (no flares or dose escalation) * On or off second-line agent * \> 18 years old * Written informed consent provided
Exclusion criteria
* Cardiac or neurosarcoidosis * Advanced pulmonary sarcoidosis defined as either: (a) composite physiological index (CPI) \> 40 (b) pulmonary hypertension * Active sarcoidosis flare or dose escalation in the past 6 months * Known adrenal insufficiency * Pregnancy or breastfeeding * Previous or current infliximab use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients achieving a prednisolone dose < 50% of baseline dose | From enrolment to 6 weeks after complete steroid wean or lowest prednisolone dose achieved | To evaluate the proportion of patients achieving a prednisolone dose ≤50% of baseline utilising two tapering regimens (standard vs. fast) while maintaining clinical stability |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
| Number and length of interruptions to prednisolone taper | Enrolment until 6 weeks following complete steroid wean or lowest achieved prednisolone dose | Measurement of the number and the length of any interruptions to the prednisolone taper |
| Evaluation of changes in quality of life | See in description as insufficient space for the detail above to be entered in this section | Using the King's sarcoidosis questionnaire (KSQ) to determine any changes in quality of life with prednisolone tapering This questionnaire will be performed at: 1. Baseline visit 2. 5mg/day visit (when participant reaches 5mg/day of prednisolone (only if baseline prednisolone dose \> 5mg/day) and the exact time this will occur will vary depending on whether participant in the standard or fast taper arm) 3. 3mg/day visit (when participant reaches 3mg/day of prednisolone and the exact time this will occur will vary depending on whether participant is in the standard or fast taper arm) 4. Final visit (this will occur 6 weeks after complete wean of steroid or lowest achievable prednisolone dose) 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. |
| Proportion of patients with cortisol levels < 25nmol/L at prednisolone dose 3mg/day | This will be performed 2 weeks after reaching prednisolone dose of 3mg/day | 2 weeks following reaching prednisolone dose of 3mg/day, morning blood cortisol level will be taken |
| Assess for symptoms of steroid withdrawal, safety and tolerability with prednisolone weaning | See in description as insufficient space for the detail above to be entered in this section | Using Addison's Disease (AD) quality of life questionnaire (AddiQoL) to determine if any symptoms of steroid withdrawal This questionnaire will be performed at: 1. Baseline visit 2. 5mg/day visit (when participant reaches 5mg/day of prednisolone (only if baseline prednisolone dose \> 5mg/day) and the exact time this will occur will vary depending on whether participant in the standard or fast taper arm) 3. 3mg/day visit (when participant reaches 3mg/day of prednisolone and the exact time this will occur will vary depending on whether participant is in the standard or fast taper arm) 4. Final visit (this will occur 6 weeks after complete wean of steroid or lowest achievable prednisolone dose) 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). |
| Evaluation of prednisolone dose | See in description as insufficient space for the detail above to be entered in this section | Prednisolone dose will be recorded at: 1. Final visit (this is defined as 6 weeks post complete steroid wean or lowest achievable steroid dose, due to 2 different steroid tapering regimens this will vary between participants) 2. 12 months post randomisation (randomisation occurs at baseline visit in all patients) (this is not a study visit but participants will be consented for medical notes to be accessed at this time point) |
| Changes in body composition measured with bioimpedance analysis (BIA) | BIA will be performed at the baseline visit and final visit (6 weeks following complete steroid wean or lowest achieved steroid dose). | 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. |
| Change in body composition using isometric quadriceps testing strength | This will be performed at baseline and final visit (6 weeks following complete prednisolone wean or lowest achieved prednisolone dose). | In a subset of 30 patients (15 in each arm) we will be performing isometric quadriceps testing. |
| Changes in body composition using 5 times sit to stand test (5STS) | 5STS will be performed at baseline and final visit (6 weeks following complete steroid wean or lowest achieved steroid dose). | This test will be performed in a subset of 30 patients (15 in each arm). The 5STS is a functional test assessing quadricep strength. |
| Evaluation of changes in quality of life and fatigue | See in description as insufficient space for the detail above to be entered in this section | Using the fatigue assessment scale (FAS) to determine any changes in quality of life with prednisolone tapering This questionnaire will be performed at: 1. Baseline visit 2. 5mg/day visit (when participant reaches 5mg/day of prednisolone (only if baseline prednisolone dose \> 5mg/day) and the exact time this will occur will vary depending on whether participant in the standard or fast taper arm)\* 3. 3mg/day visit (when participant reaches 3mg/day of prednisolone and the exact time this will occur will vary depending on whether participant is in the standard or fast taper arm) 4. Final visit (this will occur 6 weeks after complete wean of steroid or lowest achievable prednisolone dose) 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 |
Countries
United Kingdom
Contacts
CONTACTVasileios Kouranos
CONTACTJessica Raja
PRINCIPAL_INVESTIGATORVasileios Kouranos
Interstitial Lung Disease Department, Royal Brompton Hospital
Outcome results
None listed