Contact information
Type
Scientific
Primary contact
Dr E.H. Hoogendoorn
ORCID ID
Contact details
UMCN st Radboud
Dept Endocrinologie
huispost 531
P.O. Box 9101
Nijmegen
6500 HB
Netherlands
+31 (0)24 3614599
E.Hoogendoorn@ENDO.umcn.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NTR75
Study information
Scientific title
Acronym
SUBstudy / SUBstudie
Study hypothesis
To provide evidence that restoration of euthyroidism (normal TSH) improves thyrotoxic symptoms and signs and quality of life and lowers the risk of subsequent atrial fibrillation and bone loss in subjects with endogenous subclinical hyperthyroidism.
Ethics approval
Received from local medical ethics committee
Study design
Multicentre randomised single blind active controlled parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Not Specified
Patient information sheet
Condition
Thyrotoxic symptoms, nodular goiter, hyperthyroidism
Intervention
Randomised clinical trial comparing active treatment with 131I with no treatment in subjects with endogenous subclinical hyperthyroidism in a multicenter study.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measures
1. Progression to overt hyperthyroidism: TSH, fT4, T3 every year
2. Changes in (thyrotoxic) symptoms (null-hypothesis: radioiodine does not cause improvement):
2.1. Quality of life - short form 36 Health Survey: on T=0, T=2 and T=5 years
2.2. Modified hyperthyroid symptom scale: on T=0, T=2 and T=5 years
2.3. In the treatment group on T= 1 year: duration of admission to hospital for administration of I131 (if necessary) and signs or symptoms of iodine induced thyroiditis or Graves like disease following iodine treatment making medical treatment necessary
3. Cardiac changes (null-hypothesis: radioiodine does not prevent development of atrial fibrillation):
3.1. 12-lead ECG: on T=0, T=2 and T=5 years
3.2. Holter monitoring (24 hour): mean 24-hour heart rate, number of PAC and
VES: on T=0, T=2 and T=5 years
4. Changes in bone mineral density (null-hypothesis: radioiodine does not prevent
deterioration of BMD): DEXA (Hologic or Lunar) L1-L4 and (right) femoral neck): on
T=0, T=2 and T=5 years
Secondary outcome measures
Not provided at time of registration
Overall trial start date
01/06/2003
Overall trial end date
01/06/2010
Reason abandoned
Eligibility
Participant inclusion criteria
1. Subclinical hyperthyroidism [TSH <= 0.1 mU/L, fT4 and T3 within the normal range of the own laboratory (determined 2 times in own laboratory with an interval of at
least 2 months)
2. Endogenous cause of subclinical hyperthyroidism limited to autonomous adenoma or multinodular goiter (diagnosis made by the attending physician, based on palpation and the result of a thyroid scintigram)
3. Informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
192
Participant exclusion criteria
1. Medication with anti-thyroid drugs in the last 3 months (also not allowed during follow-up), thyroid hormone in the last 3 months (allowed during follow-up, but TSH levels should be kept between 0.1 mU/L and the upper limit of normal in the own laboratory) and oral glucocorticoids in the last 3 months (allowed during follow-up when absolutely necessary, but patients in whom glucocorticoids are
started cannot be evaluated with respect to changes in BMD).
2. Radioiodine therapy in the past
3. Iodine-induced subclinical hyperthyroidism
4. Pituitary or hypothalamic insufficiency
5. Pregnancy
6. Age <= 50 years and > 80 years
7. Severe non-thyroidal illness
8. Drug abuse
9. Unstable angina pectoris, (history of) atrial fibrillation, (history of) congestive heart failure.
10. (History of) osteoporotic fracture(s)
11. Patients younger than 70 years of age with a bone mineral density T-score <2.5
SD, or older than 70 years of age with a bone mineral density Z-score <-1.0 SD
12. These patients can be randomised but in case it is decided to treat them with antiosteoporotic drugs they cannot be evaluated with respect to changes in BMD.
13. Use of betablockers in the last three months. These patients can be randomised but cannot be evaluated with respect to
general and cardiac symptoms. The same applies to patients in whom betablockers are started during follow up.
14. Other symptoms or signs of hyperthyroidism or obstruction of vital structures which in the opinion of the attending physician urge to active treatment.
Recruitment start date
01/06/2003
Recruitment end date
01/06/2010
Locations
Countries of recruitment
Netherlands
Trial participating centre
UMCN st Radboud
Nijmegen
6500 HB
Netherlands
Sponsor information
Organisation
University Medical Centre St Radboud (Netherlands)
Sponsor details
Centraal Geert Groteplein 10
P.O. Box 9101
Nijmegen
6500 HB
Netherlands
+31 (0)24 3619166
PIPmail@po.umcn.nl
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
University Medical Centre St. Radboud (Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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