rhTSH, Radioiodine Uptake and Goiter Reduction Following 131I Therapy in Patients With Benign Nontoxic Nodular Goiter

The Effect of 0.1 mg Recombinant Human Thyrotropin (rhTSH) on Thyroid Radioiodine-uptake and the Degree of Goiter Reduction Following 131I-therapy, in Patients With Benign Non-toxic Nodular Goiter. A Randomized, Double-blind, Placebo-controlled Trial.

The study aims at clarifying (in a randomized, double-blinded design):

1. Whether stimulation with 0.1 mg rhTSH 24, 48 or 72 hours before induction of a 131I-tracer dosis increases the 131I uptake in patients with atoxic multinodular goitre and to study which time interval is the most optimal (Part I)
2. Whether patients suffering from atoxic multinodular goitre obtains a corresponding goitre reduction compared with a control group when stimulating with 0.1 mg rh TSH 24, 48 or 72 hours before 131I therapy and when reducing the thyroid radiation dose to 50 Gy (Part II)

The two studies will be carried out successively on the same patient population. The 131I uptake will be carried out first followed by the I therapy itself. The patients are compared with a placebo-treated control group going through the same course of treatment, but the 131I dosis will be 100 Gy (standard treatment). After the 131I therapy, all patients are followed during one year with a regular ultrasound scan of the thyroid gland and control of the metabolic status. The patient satisfaction is monitored by the use of a visual-analogue-scale.

Study Overview

• Status: Completed
• Conditions: Nodular Goiter
• Intervention / Treatment: Drug: Recombinant human thyrotropin (Thyrogen); Drug: recombinant human TSH; Other: isotonic saline = placebo

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age over 18 years
• Apart from benign non-toxic goiter no other serious illness
• Signed proof of participation

Exclusion Criteria:

• Treatment with Levothyroxine
• Former 131I-therapy
• A thyroid volume above 100 ml or a retro-clavicular component
• Unsafe contraception
• Pregnancy or breastfeeding
• Participation in another clinical trial
• Previous allergic reaction toward rhTSH
• Suspicion of malignancy in the thyroid gland either by clinical examination, laboratory findings (a raised serum calcitonin or ionized calcium)or by fine-needle aspiration biopsy
• Physically or mental condition making it impossible to participate
• Acute ischemic heart attach within the last 3 months
• Alcohol and/or drug addicts

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: rhTSH; proceeded by 0.1 mg rhTSH	Drug: Recombinant human thyrotropin (Thyrogen); 0.1 mg rhTSH administered intramuscularly; Drug: recombinant human TSH; 0.1 mg rhTSH administered intramuscularly
Placebo Comparator: Placebo; 1 ml isotonic saline	Other: isotonic saline = placebo; 0.1 mg isotonic saline injected intramuscularly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
An intra-individual comparison of the thyroid 131I-uptake before and after stimulation with rhTSH /placebo	24 and 96 hours after tracer administration
An inter-individual comparison of the thyroid 131I uptake between those who receive placebo and those who receive rhTSH	24 and 96 hours after tracer administration
An estimation of which time-interval, injecting rhTSH, that is more favourable before 131I therapy (24 hours, 48 hours or 72 hours)	24 and 96 hours after tracer administration
A comparison of the degree of goiter reduction when patients are prestimulated with rhTSH and receive a thyroid 131I dose of 50 Gy or when receiving conventional 131I, receiving a thyroid dose of 100 Gy	3, 6, 9 and 12 months after 131I therapy

Secondary Outcome Measures

Outcome Measure	Time Frame
A registration of adverse effects following rhTSH/placebo	All adverse effects occuring within one year follow-up
Patient satisfaction (Visual Analogue Scale) before, 3 months post 131I therapy, and at the end of follow-up (1 year).	baseline, 3 and 12 months after 131I therapy
Development of TPOab or TSHRab	At 12 months follow-up
Thyroid function	At 12 months follow up.

Collaborators and Investigators

• Sponsor: Steen Bonnema
• Investigators: Principal Investigator: Steen J. Bonnema, MD, Odense University Hospital

Publications and helpful links

General Publications

• Huo Y, Xie J, Chen S, Wang H, Ma C. Recombinant human thyrotropin (rhTSH)-aided radioiodine treatment for non-toxic multinodular goitre. Cochrane Database Syst Rev. 2021 Dec 28;12:CD010622. doi: 10.1002/14651858.CD010622.pub2. Review.
• Fast S, Hegedus L, Grupe P, Nielsen VE, Bluhme C, Bastholt L, Bonnema SJ. Recombinant human thyrotropin-stimulated radioiodine therapy of nodular goiter allows major reduction of the radiation burden with retained efficacy. J Clin Endocrinol Metab. 2010 Aug;95(8):3719-25. doi: 10.1210/jc.2010-0634. Epub 2010 Jun 2.

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: January 9, 2006
• First Submitted That Met QC Criteria: January 9, 2006
• First Posted (Estimate): January 11, 2006

Study Record Updates

• Last Update Posted (Estimate): December 4, 2013
• Last Update Submitted That Met QC Criteria: December 3, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Nontoxic nodular goiter; 131I therapy; thyroid radioiodine uptake; optimal time-interval; reduced 131I activity; goiter reduction
• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Goiter; Goiter, Nodular
• Other Study ID Numbers: 019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No