Fatigue and Sarcoidosis: Treatment with Methylphenidate

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2016-000342-60-GB
• Date of registration: 06/02/2019
• Prospective Registration: No
• Primary sponsor: Norfolk and Norwich University Hospital
• Public title: Fatigue and Sarcoidosis: Treatment with Methylphenidate
• Scientific title: Fatigue in Sarcoidosis - A feasibility study investigating the treatment of fatigue in stable sarcoidosis patients using methylphenidate - Fatigue in Sarcoidosis: Treatment with Methylphenidate
• Date of first enrolment: 21/06/2016
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000342-60
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Lisa Chalkley
• Affiliation: Norfolk and Norwich University Hospital NHS Foundation Trust

• Name: Lisa Chalkley
• Affiliation: Norfolk and Norwich University Hospital NHS Foundation Trust

Key inclusion & exclusion 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:
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).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: Methylphenidate
Product Name: Methylphenidate 10mg tablets
Product Code: NA
Pharmaceutical Form: Tablet
INN or Proposed INN: Methylphenidate
CAS Number: 113-45-1
Current Sponsor code: None
Other descriptive name: None
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: The evaluations of feasibility are made at 2,4,6,12,18 and 24 weeks.

Primary end point(s): This is a feasibility study - the outcome measures regarding this are viewed with equal importance and are therefore not divided into primary and secondary objectives.

The assessments of feasibility are:
(1) What is the recruitment rate of participants? (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) What is the retention rate of participants within 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 included and continuing the trial representative of sarcoidosis cohorts?)
(5) How often are patients suffering side effects from the medication and how many participants discontinuing the medication during the study trial? (see assessment of safety below)
(6) Is the effect of methylphenidate sustained over the whole 24 weeks of the trial? (does the future trial need to be as long? Is 8-12 weeks an acceptable study length?)
(7) Do participants complete assessments during the trial? (Can we capture the data that we need? - and which of the assessments collect the data that we need)
(8) Will participants wear accelerometer devices on their wrist (like a wrist watch) to measure their activity levels and can adequate data be reliably obtained from these devices? (will enough patients remember to use the accelerometers for the required minimum four days out of the seven day period?)
(9) Acceptability of number of study visits and assessments
(10) Acceptability of randomisation to active drug or placebo.
(11) Acceptability of receiving a stimulant medication.
(12) Estimate of size of effect of the medication (to plan future sample size)

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 during a fixed time)
(6) Lung function (breathing tests)
(7) Physical activity over a 7 day period (measured using a wrist-worn accelerometer, a small device the size of a wrist watch that measures how active a person is)

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 Outcome(s)

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 weeks

Secondary ID(s)

NCT02643732

190280

Source(s) of Monetary Support

National Institute of Health Research

Ethics review

Status: Approved
Approval date:
Contact: