Condition category
Nutritional, Metabolic, Endocrine
Date applied
06/01/2010
Date assigned
15/05/2013
Last edited
14/06/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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 one’s 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 participant’s 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

Contact information

Type

Scientific

Primary contact

Prof Julia Newton

ORCID ID

Contact details

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

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

http://www.newcastle-hospitals.org.uk/

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

Publication citations

Additional files

Editorial Notes

14/06/2016: No publications found, verifying study status with principal investigator.