Fatigue In Subclinical Hypothyroidism

ISRCTN	ISRCTN70749570
DOI	https://doi.org/10.1186/ISRCTN70749570
Secondary identifying numbers	N/A

Submission date: 06/01/2010
Registration date: 15/05/2013
Last edited: 22/02/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Having a mild underactive thyroid (thyroid gland not producing enough hormone) is a common medical condition affecting 5-10% of the general population. Fatigue and problems relating to ones thought process (cognitive symptoms) are frequently reported in patients with this condition. It is unclear whether these symptoms are caused by the underactive thyroid. The study aims to find out the mechanisms of fatigue and cognitive symptoms in patients with this condition.

Who can participate?
We aim to recruit 20 patients with mild thyroid underactive state (men or women, aged between 18 and 65 years) and 20 healthy volunteers who will act as control.

What does the study involve?
Patients and healthy volunteers will undergo preliminary clinical assessment. If they are eligible, then they will have a series of tests. These involve magnetic resonance imaging scans (MRI scans) of the brain, heart and leg muscle; assessing heart rate and blood pressure over a period of 2 hours; and psychometric tests for intelligence, reading and memory. The patients will have these tests again after being given thyroxine treatment for 6 months.

What are the possible benefits and risks of participating?
Participants may or may not benefit personally by taking part in this study. But the results may eventually change how we manage fatigue in the future and therefore have benefits for others.
The study involves a series of assessments, which means we will be asking for a significant amount of time. Furthermore, there is a very small possibility that during the tests we may discover an incidental abnormality that we have not expected. If this is the case we will liaise with the participants doctor in order to ensure that any appropriate action is taken. Patients may experience mild side-effects from thyroxine treatment if they take too much, but this is monitored closely.

Where is the study run from?
The study has been set up by Gateshead Health NHS Trust, Gateshead, UK.

When is the study starting and how long is it expected to run for?
January 2010 to January 2012

Who is funding the study?
BUPA Foundation (UK)

Who is the main contact?
Prof Julia Newton
Julia.Newton@ncl.ac.uk

Contact information

Prof Julia Newton
Scientific

FASS unit
Leazes Wing
Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4LP
United Kingdom

Study information

Study design	Single centre open label trial
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Investigating the mechanisms of muscle fatigue and cognitive symptoms in subclinical hypothyroidism
Study acronym	FISH
Study objectives	Individuals with subclinical hypothyroidism (SCH) have fatigue due to a combination of cerebral, cardiac and skeletal muscle abnormalities as well as autonomic dysfunction and that this fatigue is (partly or fully) reversible with treatment.
Ethics approval(s)	Newcastle & North Tyneside 2 Research Ethics Committee approved on the 20/08/2009, ref: NO-08/H0907/53
Health condition(s) or problem(s) studied	Subclinical hypothyroidism
Intervention	All patients are treated with tablet thyroxine for 6 months, at a dose of 1.6 µg/Kg, titrated 6 - 8 weekly, to attain a TSH of 1 - 1.5 mU/L.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Thyroxine
Primary outcome measure	1. Brain magnetic resonance imaging (MRI) - regional cerebral blood flow and activation of specific regions of intererest during N-back testing at baseline and 6 months 2. Muscle MRI - during rest, exercise and recovery-muscle pH, pH recovery, phosphocreatinine and recovery, inorganic phosphate/adenosine tri-phosphate (ATP) ratio at baseline and 6 months 3. Cardiac MRI - phosphocreatinine/ATP ratio at rest at baseline and 6 months 4. Autonomic function tests at baseline and 6 months: 4.1. Active standing for 3 minutes 4.2. Valsalva's manoeuver 4.3. Tilt testing - 40 minutes 4.4. Heart rate variability (HRV) - time and frequency domain analysis during rest, during and recovery from above manoeuvers 5. Psychometric questionnaires at baseline and 6 months: 5.1. Wechsler Abbreviated Scale of Intelligence (WASI) 5.2. Wechsler Test of Adult Reading (WTAR) 5.3. The Controlled Oral Word Association Test 5.4. Wechsler Memory Scale-III abbreviated (WMS) 6. Fatigue Impact Symptom Score at baseline and 6 months 7. Thyroid Symptom Check List and quality of life questionnaires at baseline and 6 months
Secondary outcome measures	No secondary outcome measures
Overall study start date	07/01/2010
Completion date	10/01/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	30
Key inclusion criteria	1. Aged 18 to 65 years 2. Subjects with confirmed SCH thyroid stimulating hormone (TSH) between 4.1 and 10.0 for more than 3 months 3. Fatigue Impact Score greater than 40
Key exclusion criteria	1. Subjects with previous thyroid disease or on thyroid hormone replacement, anti-thyroid drugs, oral contraceptive pill (OCP), hypotensive agents, aspirin, statins or angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blocker 2. Subjects with known diabetes mellitus/impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) 3. Known renal failure or a serum creatinine greater than 120 µmol/l within the past 3 months 4. Previous participation in a clinical trial within the past month 5. Previous history of vascular/heart disease 6. Malignancy (any) 7. Active infections 8. Body mass index (BMI) greater than 35 9. Psychiatric disease 10. Drug abuse 11. Previous major head injuries/epilepsy 12. Pacemakers/cerebral aneurysm clips 13. Pregnancy
Date of first enrolment	07/01/2010
Date of final enrolment	10/01/2012

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

FASS unit

Newcastle upon Tyne
NE1 4LP
United Kingdom

Sponsor information

Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

c/o Dr Lesley Hall, PhD
Research and Development Manager
Joint Research Office
4th Floor Leazes Wing
Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
England
United Kingdom

Website	http://www.newcastle-hospitals.org.uk/
"ROR"	https://ror.org/05p40t847

Funders

Funder type

Charity

BUPA Foundation (UK) (ref: 22094167)
Private sector organisation / Trusts, charities, foundations (both public and private)

Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration 2016 results published in thesis https://theses.ncl.ac.uk/dspace/handle/10443/3242
IPD sharing plan

Editorial Notes

22/02/2019: Thesis added to publication and dissemination plan.
14/06/2016: No publications found, verifying study status with principal investigator.