Fatigue in Sarcoidosis - A Feasibility Study Investigating the Treatment of Fatigue in Stable Sarcoidosis Patients Using Methylphenidate
试验速览
- 阶段
- 不适用
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of accelerometers returned with valid data (Feasibility outcome)
研究概览
简要总结
This is a small randomised-controlled trial (RCT) using methylphenidate as a treatment for clinically-significant fatigue in sarcoidosis patients with stable disease. The primary outcomes are feasibility, aimed at determining factors that will influence the design a future, larger RCT, which will be powered to look at clinical efficacy of the intervention.
详细描述
Sarcoidosis and fatigue
Sarcoidosis is a systemic granulomatous disease that affects all ethnic groups and ages. In the United Kingdom the incidence of the disease is 5.0 cases per 100,000 patient years, with a mean age at diagnosis of 47 years, frequently affecting patients of working age(Gribbin et al). The cause is unknown and there is no cure(Iannuzzi et al). Many patients suffer from debilitating fatigue for which there is presently no treatment.
Fatigue has been described as a "core symptom" of sarcoidosis, and is present in up to 80% of patients(Marcellis et al). A "post-sarcoidosis chronic-fatigue syndrome" has been described(James), denoting the presence of fatigue where there is no evidence of active disease. The presence of this symptom has been shown to adversely affect quality of life(Michielsen et al). Although there increased risk of obstructive sleep apnoea and sleep-disordered breathing occurring in sarcoidosis patients(Michielsen et al; Drent et al) the majority of patients have no identifiable cause for fatigue other than their sarcoidosis.
Both the British Thoracic Society(Bradley et al) and American Thoracic Society(Costabel et al) produce guidelines for physicians treating people with sarcoidosis. Neither guideline gives any advice on treatment of fatigue. Fatigue is a common problem in sarcoidosis. In a study of 76 patients with sarcoidosis, 50.7% reported pathological levels of fatigue, defined as a Fatigue Assessment Scale (FAS) score of greater than 21 units, compared with 8.6% of controls. People reporting fatigue scores above 21, had poorer EuroQoL Visual Analogue Scale (EQVAS) scores compared with people reporting fatigue scores of 21 or below (mean scores 0.561 vs 0.792 , p<0.001) (Unpublished data, Norfolk and Norwich University Hospital). This shows that fatigue impacts upon quality of life in sarcoidosis.
Methylphenidate - a treatment for fatigue
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Biopsy-proven diagnosis of sarcoidosis or diagnosis of sarcoidosis from interstitial lung disease multidisciplinary team meeting after review of radiological and clinical information
- •Stable disease (treatment unchanged for 6 weeks, without anticipation of treatment change during trial period)
- •FAS score greater than 21 units
- •Able to give informed consent
- •In patients on warfarin therapy - Willing to consent to increased frequency of monitoring
排除标准
- •Evidence of co-existing obstructive sleep apnoea. Patients screened with a "STOP-Bang" questionnaire (acronym taken from individual questions within the questionnaire itself) score of greater than 4 must undertake overnight oximetry; they are excluded if this shows a desaturation index of more than 15 events per hour on overnight oximetry.
- •Documented history of significant cardiac disease (including cardiac sarcoid) OR associated disease which would increase risk of underlying coronary artery disease (cerebrovascular disease, previous stroke or peripheral vascular disease). Definitively treated cardiac disease e.g. previous myocardial infarction treated with stents or coronary artery bypass grafting with no ongoing symptoms is permitted.
- •Hyperthyroidism evidenced by abnormal screening thyroid function tests (Thyroid stimulating hormone level outside normal range of 0.35 - 3.50 milliunits/litre (mU/L) or thyroxine (T4) outside normal range of 8 - 21 picomoles per litre (pmol/L)).
- •History of seizures, excluding febrile convulsions whilst an infant.
- •Abnormal electrocardiogram (ECG) with evidence of arrhythmia (except first degree heart block which has been stable for 3 months).
- •Concomitant therapy with the following drugs:
- •Tricyclic antidepressants
- •Monoamine oxidase inhibitors
- •Tramadol or buprenorphine
- •Haloperidol and atypical antipsychotics
- •Glaucoma or raised intra-ocular pressure for any reason.
- •Patients with established liver disease defined as Child-Pugh class B or C.
- •Documented medical history of psychiatric disorders (excluding depression)
- •History of drug-dependence or addiction at any time
- •Female participant who is pregnant, lactating or planning pregnancy during the course of the trial
- •Female patient of childbearing potential unable or unwilling to take two acceptable forms of contraception (see exclusions section)
- •Receiving an investigational drug or biological agent within 6 weeks (or 5 times the half-life if this is longer) prior to study entry.
研究组 & 干预措施
Methylphenidate
Methylphenidate 10mg (one tablet) twice daily, increasing to 20mg (two tablets) twice daily following assessment 2 weeks into trial.
24 weeks duration
干预措施: Methylphenidate (overencapsulated) (Drug)
Placebo
Identical, over-encapsulated placebo tablets manufactured to be identical to the experimental tablets. One tablet twice daily, increased to two tablets twice daily following assessment 2 weeks into trial.
24 weeks duration.
干预措施: Placebo (Over-encapsulated tablet) (Drug)
结局指标
主要结局
Number of accelerometers returned with valid data (Feasibility outcome)
时间窗: 24 weeks (trial duration)
Accelerometers are a novel outcome in this study. Their use in a trial of this nature has not been performed before. We wish to see how many participants return the accelerometer devices at the three time points in the trial, and how many of these have valid data on them; this is defined as 4 or more days of use with 10 or more hours or data. It is designed to see if it is feasible to use these devices as an outcome measure in future trials.
Recruitment rate (Feasibility outcome)
时间窗: Up to 18 months (recruitment period duration)
How quickly the 30 participants are recruited to the study (relates to feasibility criteria regarding number of centres that are likely to be needed in a future, larger randomised controlled trial). Up to 18 months is allowed for recruitment, based on 2 years for trial to be run and 24 weeks for final patient to complete study.
Side-effect rate (Feasibility and Safety outcome)
时间窗: 24 weeks (trial duration)
Number of participants reporting side effects; what they are, severity and need for discontinuation of study drug all required. A likert scale measuring specific symptoms (palpitations, insomnia, headaches and chest pains) is also administered and these results will be recorded and presented to see if there are differences between the two groups. Participants also have an ECG at all study visits; any change in ECG will be recorded and the number of participants required to discontinue medications will be recorded.
Number of potential participants excluded (Feasibility outcome)
时间窗: Up to 18 months (recruitment period duration)
A record of the number of participants screened for inclusion will be kept, including whether they entered the trial or not, and if they were excluded, for what reason(s) they were excluded. This relates to number of centres likely to be required for a future trial. Up to 18 months is allowed for recruitment, based on 2 years for trial to be run and 24 weeks for final patient to complete study.
Number of participants dropping out/Participant retention rate (Feasibility outcome)
时间窗: 24 weeks (trial duration)
Number of participants withdrawing/dropping out of the study, including reasons where able; enables estimation of drop-out rates so that future studies can be appropriately sized, and also whether there are safety issues (side-effects necessitating withdrawals or patients not tolerating medications) that would suggest a future study is unnecessary.
Number of missed or unfilled assessments (Feasibility outcome)
时间窗: 24 weeks (trial duration)
Identifies whether appropriate data is being collected within the trial.
次要结局
- Modified Shuttle Walk Test (MSWT)(0, 12, 24 weeks)
- Short-form 36 (SF-36) Questionnaire(0,6,12,18,14 and 30 weeks)
- Hospital Anxiety and Depressions Score (HADS)(0,6,12,18,14 and 30 weeks)
- Accelerometer Use (wrist-worn accelerometer)(0, 12, 24 weeks)
- Kings Sarcoidosis Questionnaire (KSQ)(0,6,12,18,14 and 30 weeks)
- Fatigue Assessment Scale (FAS) (Clinical outcome)(0,2,4,6,12,18,14 and 30 weeks)
- Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)(0,2,4,6,12,18,14 and 30 weeks)
- EuroQoL-5D (EQ5D) Questionnaire(0,6,12,18,14 and 30 weeks)