Plain English Summary
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
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Investigating the mechanisms of muscle fatigue and cognitive symptoms in subclinical hypothryoidism
Acronym
FISH
Study hypothesis
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
Newcastle & North Tyneside 2 Research Ethics Committee approved on the 20/08/2009, ref: NO-08/H0907/53
Study design
Single centre open label trial
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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
Phase
Not Applicable
Drug names
Thyroxine
Primary outcome measures
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 trial start date
07/01/2010
Overall trial end date
10/01/2012
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
30
Participant 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
Recruitment start date
07/01/2010
Recruitment end date
10/01/2012
Locations
Countries of recruitment
United Kingdom
Trial participating centre
FASS unit
Newcastle upon Tyne
NE1 4LP
United Kingdom
Sponsor information
Organisation
Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
Sponsor details
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
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Charity
Funder name
BUPA Foundation (UK) (ref: 22094167)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
foundation
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary