Condition category
Nutritional, Metabolic, Endocrine
Date applied
12/09/2005
Date assigned
12/09/2005
Last edited
24/08/2009
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

Publication citations

Additional files

Editorial Notes