Fatigue in Sarcoidosis - Treatment With Methylphenidate

NCT02643732 | Unknown DMC

• 1 other identifier: 170-11-15
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sarcoidosis; Fatigue

Keywords

Activity

Outcome Measures

Primary Outcomes (6)

• Recruitment rate (Feasibility outcome)

  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.

  Up to 18 months (recruitment period duration)

• Number of potential participants excluded (Feasibility outcome)

  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.

  Up to 18 months (recruitment period duration)

• Number of participants dropping out/Participant retention rate (Feasibility outcome)

  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.

  24 weeks (trial duration)

• Side-effect rate (Feasibility and Safety outcome)

  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.

  24 weeks (trial duration)

• Number of missed or unfilled assessments (Feasibility outcome)

  Identifies whether appropriate data is being collected within the trial.

  24 weeks (trial duration)

• Number of accelerometers returned with valid data (Feasibility outcome)

  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.

  24 weeks (trial duration)

Secondary Outcomes (8)

• 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

• Kings Sarcoidosis Questionnaire (KSQ)

  0,6,12,18,14 and 30 weeks

• EuroQoL-5D (EQ5D) Questionnaire

  0,6,12,18,14 and 30 weeks

• Short-form 36 (SF-36) Questionnaire

  0,6,12,18,14 and 30 weeks

Other Outcomes (1)

• Health Economic/Utility Use

  0, 12, 24 weeks

Study Arms (2)

Methylphenidate

EXPERIMENTAL

Methylphenidate 10mg (one tablet) twice daily, increasing to 20mg (two tablets) twice daily following assessment 2 weeks into trial. 24 weeks duration

Drug: Methylphenidate (overencapsulated)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo (Over-encapsulated tablet)

Interventions

Methylphenidate (overencapsulated) DRUG

10mg (1 capsule) methylphenidate (standard release) twice daily, increased to 20mg (2 capsules) twice daily after 2 weeks. The drug can be down-titrated in the event of side effects, although re-uptitration is not allowed even if the side effects resolve on the lower dose.

Also known as: Tranquilyn

Methylphenidate

Placebo (Over-encapsulated tablet) DRUG

Identical capsules (over-encapsulated placebo tablets), administered initially one capsule twice daily, increased to 2 capsules after 2 weeks. As with the methylphenidate arm, the dose can be down-titrated in the event of side effects, although re-uptitration is not allowed even if the side effects resolve on the lower dose.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Levodopa
• 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

Sponsors & Collaborators

• University of East Anglia: lead
• Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK): collaborator

Study Sites (1)

Norfolk and Norwich University Hospital

Norwich, Norfolk, NR4 7UY, United Kingdom

RECRUITING

Related Publications (20)

• Gribbin J, Hubbard RB, Le Jeune I, Smith CJ, West J, Tata LJ. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax. 2006 Nov;61(11):980-5. doi: 10.1136/thx.2006.062836. Epub 2006 Jul 14.

  PMID: 16844727 BACKGROUND

• Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007 Nov 22;357(21):2153-65. doi: 10.1056/NEJMra071714. No abstract available.

  PMID: 18032765 BACKGROUND

• Marcellis RG, Lenssen AF, Elfferich MD, De Vries J, Kassim S, Foerster K, Drent M. Exercise capacity, muscle strength and fatigue in sarcoidosis. Eur Respir J. 2011 Sep;38(3):628-34. doi: 10.1183/09031936.00117710. Epub 2011 Mar 24.

  PMID: 21436356 BACKGROUND

• James DG. Complications of sarcoidosis. Chronic fatigue syndrome. Sarcoidosis. 1993 Mar;10(1):1-3.

  PMID: 8134708 BACKGROUND

• Michielsen HJ, Drent M, Peros-Golubicic T, De Vries J. Fatigue is associated with quality of life in sarcoidosis patients. Chest. 2006 Oct;130(4):989-94. doi: 10.1378/chest.130.4.989.

  PMID: 17035429 BACKGROUND

• Turner GA, Lower EE, Corser BC, Gunther KL, Baughman RP. Sleep apnea in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1997 Mar;14(1):61-4.

  PMID: 9186990 BACKGROUND

• Drent M, Verbraecken J, van der Grinten C, Wouters E. Fatigue associated with obstructive sleep apnea in a patient with sarcoidosis. Respiration. 2000;67(3):337-40. doi: 10.1159/000029523.

  PMID: 10867608 BACKGROUND

• Bradley B, Branley HM, Egan JJ, Greaves MS, Hansell DM, Harrison NK, Hirani N, Hubbard R, Lake F, Millar AB, Wallace WA, Wells AU, Whyte MK, Wilsher ML; British Thoracic Society Interstitial Lung Disease Guideline Group, British Thoracic Society Standards of Care Committee; Thoracic Society of Australia; New Zealand Thoracic Society; Irish Thoracic Society. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax. 2008 Sep;63 Suppl 5:v1-58. doi: 10.1136/thx.2008.101691. No abstract available.

  PMID: 18757459 BACKGROUND

• Costabel U, Hunninghake GW. ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis Statement Committee. American Thoracic Society. European Respiratory Society. World Association for Sarcoidosis and Other Granulomatous Disorders. Eur Respir J. 1999 Oct;14(4):735-7. doi: 10.1034/j.1399-3003.1999.14d02.x. No abstract available.

  PMID: 10573213 BACKGROUND

• Keating GM, Figgitt DP. Dexmethylphenidate. Drugs. 2002;62(13):1899-904; discussion 1905-8. doi: 10.2165/00003495-200262130-00009.

  PMID: 12215063 BACKGROUND

• Volkow ND, Fowler JS, Wang G, Ding Y, Gatley SJ. Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord. 2002;6 Suppl 1:S31-43. doi: 10.1177/070674370200601s05.

  PMID: 12685517 BACKGROUND

• Lower EE, Fleishman S, Cooper A, Zeldis J, Faleck H, Yu Z, Manning D. Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. J Pain Symptom Manage. 2009 Nov;38(5):650-62. doi: 10.1016/j.jpainsymman.2009.03.011.

  PMID: 19896571 BACKGROUND

• Minton O, Richardson A, Sharpe M, Hotopf M, Stone P. Drug therapy for the management of cancer-related fatigue. Cochrane Database Syst Rev. 2010 Jul 7;2010(7):CD006704. doi: 10.1002/14651858.CD006704.pub3.

  PMID: 20614448 BACKGROUND

• Breitbart W, Rosenfeld B, Kaim M, Funesti-Esch J. A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease. Arch Intern Med. 2001 Feb 12;161(3):411-20. doi: 10.1001/archinte.161.3.411.

  PMID: 11176767 BACKGROUND

• Butler JM Jr, Case LD, Atkins J, Frizzell B, Sanders G, Griffin P, Lesser G, McMullen K, McQuellon R, Naughton M, Rapp S, Stieber V, Shaw EG. A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy. Int J Radiat Oncol Biol Phys. 2007 Dec 1;69(5):1496-501. doi: 10.1016/j.ijrobp.2007.05.076. Epub 2007 Sep 14.

  PMID: 17869448 BACKGROUND

• Lower EE, Harman S, Baughman RP. Double-blind, randomized trial of dexmethylphenidate hydrochloride for the treatment of sarcoidosis-associated fatigue. Chest. 2008 May;133(5):1189-95. doi: 10.1378/chest.07-2952. Epub 2008 Feb 8.

  PMID: 18263672 BACKGROUND

• Holland AE, Dowman L, Fiore J Jr, Brazzale D, Hill CJ, McDonald CF. Cardiorespiratory responses to 6-minute walk test in interstitial lung disease: not always a submaximal test. BMC Pulm Med. 2014 Aug 11;14:136. doi: 10.1186/1471-2466-14-136.

  PMID: 25113781 BACKGROUND

• Korenromp IHE, Heijnen CJ, Vogels OJM, van den Bosch JMM, Grutters JC. Characterization of chronic fatigue in patients with sarcoidosis in clinical remission. Chest. 2011 Aug;140(2):441-447. doi: 10.1378/chest.10-2629. Epub 2011 Feb 17.

  PMID: 21330380 BACKGROUND

• Atkins C, Jones A, Clark AB, Stockl A, Fordham R, Wilson AM. Feasibility of investigating methylphenidate for the treatment of sarcoidosis-associated fatigue (the FaST-MP study): a double-blind, parallel-arm randomised feasibility trial. BMJ Open Respir Res. 2021 May;8(1):e000814. doi: 10.1136/bmjresp-2020-000814.

  PMID: 34020962 DERIVED

• Atkins C, Fordham R, Clark AB, Stockl A, Jones AP, Wilson AM. Feasibility study of a randomised controlled trial to investigate the treatment of sarcoidosis-associated fatigue with methylphenidate (FaST-MP): a study protocol. BMJ Open. 2017 Dec 4;7(12):e018532. doi: 10.1136/bmjopen-2017-018532.

  PMID: 29208618 DERIVED

MeSH Terms

Conditions

Sarcoidosis; Fatigue; Motor Activity

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Andrew M Wilson, MD

  University of East Anglia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chris Atkins, MBBS

CONTACT

01603 591594; c.atkins@uea.ac.uk

Andrew M Wilson, MD

CONTACT

01603 591257; a.m.wilson@uea.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2015
• First Posted: December 31, 2015
• Study Start: November 1, 2016
• Primary Completion: May 1, 2018
• Study Completion: July 1, 2018
• Last Updated: January 11, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)