Sarcoidosis-associated fatigue (Patients with stable sarcoidosis and chronic fatigue) MedDRA version: 20.1 Level: PT Classification code 10039486 Term: Sarcoidosis System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Trade Name: Methylphenidate
Product Name: Methylphenidate 10mg tablets
Product Code: NA
Pharmaceutical Form: Tablet
INN or Proposed INN:
Sponsors
Norfolk and Norwich University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. A proven diagnosis of sarcoidosis – this is defined as either a biopsy-proven disease (non-caseating granulomas from a tissue biopsy), or a diagnosis of sarcoidosis agreed by an interstitial lung disease multidisciplinary team (ILD MDT) meeting. 2. Stable disease (treatment unchanged for 6 weeks, without anticipation of change in treatment during trial period) 3. Able to give informed consent. 4. Fatigue Assessment Sscale (FAS) score greater than 21 units (defined cut off for significant fatigue present) 5. In patients on warfarin therapy – Willing to consent to increased frequency of monitoring Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Evidence of co-existing obstructive sleep apnoea. Patients screened with a “STOP-Bang” questionnaire score of greater than 4 must undertake overnight oximetry; they are only excluded if this shows a desaturation index of more than 15 events per hour on overnight oximetry. Below this participants are eligible for inclusion. 2. 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. 3. Hyperthyroidism evidenced by abnormal screening thyroid function tests (TSH outside normal range of 0.35 – 3.50 mU/L or T4 outside normal range of 8 – 21 pmol/L). 4. History of seizures, excluding febrile convulsions whilst an infant. 5. Abnormal electrocardiogram (ECG) with evidence of arrhythmia (except first degree heart block which has been stable for 3 months). 6. Concomitant therapy with the following drugs: a. Tricyclic antidepressants b. Monoamine oxidase inhibitors c. Tramadol or buprenorphine d. Levodopa e. Haloperidol and atypical antipsychotics 7. Glaucoma or raised intra-ocular pressure for any reason. 8. Patients with established liver disease defined as Child-Pugh class B or C. 9. Documented medical history of psychiatric disorders (excluding depression) 10. History of drug-dependence or addiction at any time 11. Female participant who is pregnant, lactating or planning pregnancy during the course of the trial 12. Female patient of childbearing potential unable or unwilling to take two acceptable forms of contraception (see below) 13. Receiving an investigational drug or biological agent within 6 weeks (or 5 times the half-life if this is longer) prior to study entry. Exclusion criteria on pregnancy Female patients of childbearing potential and unable or unwilling to take two of the following acceptable methods of contraception for the duration of their treatment will be excluded from participating in this trial: • Established use of oral, injected or implanted hormonal methods of contraception • Barrier methods of contraception (condom or occlusive cap with spermicide – please note, use of spermicide without a form of barrier contraception is not an acceptable form of contraception) • Absolute and continuous abstinence. Periodic abstinence (calendar, ovulation, symptothermal, post-ovulation) or withdrawal are not acceptable methods of contraception For the purposes of this trial the definition of a woman of childbearing potential is a sexually mature woman (i.e. has experienced menstruation) who has not been postmenopausal for 12 consecutive months (i.e. who has had menses at any time in the last 12 months without an alternative medical cause).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The evaluations of feasibility are made at 2,4,6,12,18 and 24 weeks.; Main Objective: The primary objectives for this trial is to determine whether it is feasible to perform a suitably large randomised controlled trial investigating whether methylphenidate is a clinically effective treatment for fatigue in sarcoidosis, and how best to design this trial to successfully answer this question. As a result, the main research questions are: (1) What is the recruitment rate of participants/how quickly can we recruit people into the trial? (How many studies might need to be involved in a future trial?) (2) How many patients with sarcoidosis are excluded from the study and for what reason? (as above) (3) How many people who are included in the study manage to complete the study? (How many participants extra do we need to ensure statistical power is maintained allowing for drop-outs) (4) Why are potential participants excluded from the study, and why do participants withdraw/drop-out of the study? (as above, as well as generalisability of the results – is the population i ; Secondary Objective: Although as a feasibility study there are no primary and secondary objectives (purely questions of feasibility), data collected will be analysed for changes in the following over the 24 weeks of the trial: (1) Fatigue (using a validated fatigue score, the fatigue assessment scale (FAS)) (2) Disease-related health status (Kings' Sarcoidosis Questionnaire(KSQ)) (3) Anxiety and Depression (Hospital Anxiety and Depression Scale (HADS)) (4) Generic Quality of Life (EQ5D and SF36 questionnaires) (5) Physical capability (incremental shuttle walk test, a measured walking test performed in hospital to determine the distance able to be walked durin | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary end-points of the trial are exploratory analyses of the questionnaires and exercise assessments performed during the trial. Specifically, these are: 1. Difference in change in fatigue scores (measured by FAS and FACIT-F) 2. Difference in change in disease-specific health-related quality of life questionnaire (Kings' Sarcoidosis Questionnaire - KSQ) 3. Difference in change in depression and anxiety scores (Hospital Anxiety and Depression Scale - HADS) 4. Difference in change in generic quality of life scores (EQ5D and SF-36) 5. Use of health and social care resources (designed for this trial, elements taken from relevant tools within “Database of instruments for resource-use management” (DIRUM)). 6. Change in physical capacity (measured using Modified Shuttle Walk Test) 7. Change in level of physical activity (measured using wrist-worn accelerometer) 8. Patient perceptions of the trial, including experiences of participating in the trial (focus groups) ; Timepoint(s) of evaluation of this end point: Participants are followed up at 0,2,4,6,12,18 (postal questionnaires only) and 24 weeks. With regards to safety end-points, this data is recorded at each visit. For other end-points, data is collected at the following visits: FAS: 0,2,4,6,12,18, 24 and 30 weeks FACIT-F: 0,2,4,6,12,18,24 and 30 weeks HADS: 0,6,12,18,24,30 weeks KSQ: 0,6,12,18,24,30 weeks EQ5D: 0,6,12,18,24,30 weeks SF-36: 0,6,12,18,24,30 weeks Cost questionnaires: 0,6,12,18,24 weeks Spirometry: 0,12,24 weeks Modified shuttle walk test: 0,12,24 weeks Accelerometer measure of activity (device worn for 7 day period): -2,12,24 wee | — |
Countries
United Kingdom
Contacts
Public ContactLisa Chalkley
Norfolk and Norwich University Hospital NHS Foundation Trust
Outcome results
None listed