NEWS HIGHLIGHTS
Published Studies Related to Thyrogen (Thyrotropin)
Chromosome translocation frequency after radioiodine thyroid remnant ablation: a comparison between recombinant human thyrotropin stimulation and prolonged levothyroxine withdrawal. [2009.09]
BACKGROUND: Thyroid remnant ablation of differentiated thyroid carcinoma (DTC) patients is traditionally performed after levothyroxine withdrawal. Recombinant human TSH (rhTSH) administration increases serum TSH levels without inducing hypothyroidism. AIM: The aim of the study was to investigate the frequency of chromosome translocations in DTC patients after the first (131)I therapeutic dose and compare the frequency of translocations between DTC patients off levothyroxine and those receiving rhTSH... CONCLUSIONS: Our preliminary data show that in hypothyroid status (131)I ablation therapy induces a higher translocation rate, especially in chromosomes 4 and 8. This finding, in agreement with previous dosimetric reports, suggests that whereas inducing a low extrathyroid exposure, rhTSH reduces the potential risk of chromosomal aberration associated with blood irradiation.
Improvement of goiter volume reduction after 0.3 mg recombinant human thyrotropin-stimulated radioiodine therapy in patients with a very large goiter: a double-blinded, randomized trial. [2007.09]
INTRODUCTION: The effect of (131)I therapy amplification by recombinant human (rh) TSH prestimulation in very large goiters has not been evaluated in a double-blinded, placebo-controlled study... CONCLUSION: rhTSH-stimulated (131)I therapy improves the reduction of very large goiters by more than 50%, compared with (131)I therapy alone, but at the expense of more adverse effects after therapy. Our data suggest that rhTSH stimulation may work through mechanisms that go beyond the increase in thyroid (131)I uptake.
Peripheral blood levels of thyroglobulin mRNA and serum thyroglobulin concentrations after radioiodine ablation of multinodular goiter with or without pre-treatment with recombinant human thyrotropin. [2007.07]
We investigated the effect of therapeutic doses of radioiodine (RAI) on peripheral serum messenger thyroglobulin RNA (Tg mRNA) and serum thyroglobulin (sTg) in patients with multinodular goiter (MNG) preceded or not by treatment with recombinant human TSH (rhTSH)...
Single-dose rexinoid rapidly and specifically suppresses serum thyrotropin in normal subjects. [2007.01]
CONTEXT: Retinoid X receptor agonists (rexinoids) have demonstrated benefit in patients with certain malignancies but appear to cause central hypothyroidism in some patients with advanced cancer. The influence of rexinoids on thyroid function in healthy subjects is not clear. OBJECTIVE: The objective of this study was to determine the effect of a single dose of bexarotene on levels of TSH, T4, and T3 in healthy subjects... CONCLUSION: A single dose of a rexinoid can rapidly and specifically suppress serum TSH levels in healthy subjects. These data provide insight into the mechanisms by which rexinoids cause central hypothyroidism and potential ways this effect can be used for treatment of disorders such as thyroid hormone resistance and TSH-secreting pituitary tumors.
[Stimulation with 0,3 mg recombinant human thyrotropin (rhTSH) increases the effect of 131I therapy in patients with nontoxic nodular goiter. A prospective, randomized, double-blind trial--secondary publication] [2006.11.20]
In a randomized, double-blind, placebo-controlled trial, 57 patients with nontoxic nodular goiter were stimulated with either 0.3 mg recombinant human thyrotropin (rhTSH) or placebo before radioactive iodine 131I therapy... Patient satisfaction was high and uninfluenced by the use of rhTSH.
Clinical Trials Related to Thyrogen (Thyrotropin)
Comparison of the Safety and Successful Ablation of Thyroid Remnant in Post-Thyroidectomized Euthyroid Patients (i.e. Patients Administered Thyrogen) Versus Hypothyroid Patients (no Thyrogen) Following 131I Administration [Completed]
This study was conducted in patients with differentiated thyroid cancer who had undergone
near-total thyroidectomy. After surgery patients were randomized to one of two methods of
performing thyroid remnant ablation (use of radioiodine to remove any remaining thyroid
tissue). One group of patients who took thyroid hormone medicine and were euthyroid [i. e.
their thyroid stimulating hormone (TSH) levels are normal], and received injections of
Thyrogen (0. 9 mg daily on two consecutive days) followed by oral radioiodine. The second
group of patients did not take thyroid hormone medicine so that they were hypothyroid (i. e.
their TSH levels were high), and were given oral radioiodine. All patients received the same
amount of radioactive iodine (100 mCi or 3. 7 GBq of 131I). Approximately 8 months later,
whole body scans were performed on all patients to learn whether the thyroid remnants had
been successfully ablated. The safety profile of Thyrogen when used for radioiodine remnant
ablation also was assessed. The Quality of Life, the radioiodine uptake and retention into
the thyroid bed, as well as radiation exposure to the remainder of the body also were
assessed in both groups of patients.
A New Study to Follow-up Thyroid Cancer Patients Who Participated in a Previous Study, Which Compared the Success of Destruction of the Thyroid Remnant Using Standard Treatment or Thyrogen. [Completed]
Patients diagnosed with thyroid cancer are commonly treated with surgery to remove their
thyroid gland followed by radioiodine ablation to destroy any remaining parts of the thyroid
gland that may have been missed during surgery. It is thought that ablation with radioiodine
destroys normal remaining thyroid tissue as well as cancerous cells either in the thyroid
area or at other sites.
Following successful treatment, patients are then monitored by their physicians at regular
intervals with testing to detect any recurrence of thyroid cancer throughout the body. If
thyroid cells are detected by these follow up tests, the physician will decide the best
method to re-treat the patient.
In 2001-2003 Genzyme conducted a clinical study to test if Thyrogen® can be used to
accomplish radioiodine ablation treatment. This study aimed to determine that the success
rates of radioiodine ablation were comparable when patients were prepared for ablation with
Thyrogen® while being maintained on their normal thyroid hormone therapy, or, alternatively,
by thyroid hormone withdrawal. Thyroid hormone withdrawal commonly causes uncomfortable side
effects for patients, and these might be avoided by the use of Thyrogen.
Eight months after the initial Thyrogen plus radioiodine treatment to achieve ablation, all
patients in both groups were given Thyrogen® to test for any remaining thyroid tissue. The
results of this testing showed that all patients (in both groups) had successfully achieved
remnant ablation and had no detectable thyroid tissue remaining.
In order to confirm these remnant ablation results we will conduct follow up testing in this
study for all patients that were enrolled in the previous study and we also will determine if
their thyroid cancer has recurred. Only patients who completed this previous Thyrogen
ablation study are eligible for entry into this study.
Study of Radioiodine (131-I) Uptake Following Administration of Thyrogen and Hypothyroid States During Thyroid Hormone Withdrawal. [Completed]
Thyroid cancer is typically treated with surgery, radiation or a combination of both.
Following surgical removal of thyroid tissue patients receive thyroid hormone replacement
medication. In addition patients undergo tests to determine the status of the disease. One
of the tests conducted is a whole body scan using radioactive iodine to detect and locate any
remaining cancerous thyroid tissue.
Thyroid tissue uses iodine to make thyroid hormones (T3 and T4). In order for a radioiodine
scan to work, cancerous thyroid tissue must be "hungry" for iodine. Thyroid stimulating
hormone (TSH) produced in the pituitary gland is responsible for making thyroid tissue
"hungry" for iodine. Once thyroid tissue absorbs the radioactive iodine it will be clearly
visible on the scan and can be located for removal. However, thyroid hormone replacement
medication tends to lower the activity of the pituitary gland and the amount of naturally
produced TSH. So it is necessary to stop thyroid hormone replacement to increase TSH. A
problem arises when there is a lack of thyroid hormone replacement causing patients to
experience hypothyroidism. This condition is associated with unpleasant physical and
emotional symptoms.
TSH has been created in a laboratory and called Thyrogen. It is basically the same as the
TSH produced in the human pituitary gland. However, Thyrogen increases the level of TSH in
the body without having to stop thyroid replacement medication. Therefore patients will not
experience hypothyroidism while preparing for a radioactive iodine scan.
The objective of this study is to compare the activity of radioiodine (131I) in patients
taking Thyrogen with normal thyroid activity versus patients with hypothyroid activity after
thyroid replacement medication is withdrawn. In addition the study will provide information
on how radioactive iodine is eliminated from the body. The study will help researchers
understand how to give Thyrogen and radioiodine for purposes of scanning and therapeutic
ablation (the destruction of function) of cancerous thyroid tissue.
The study will accept patients with non-medullary thyroid cancer who are preparing for
ablation therapy. The patients will be placed in one of two groups. Group one will receive
Thyrogen in 2 doses 24 hours apart. Group two will receive Thyrogen in 3 doses 72 hours
apart. The patients will undergo two 131I whole body scans: one after Thyrogen while taking
thyroid hormone suppressive and the second after withdrawal from thyroid hormone. 131I
ablative therapy will be given under hypothyroid conditions at the completion of the study.
Study Comparing Thyrogen Versus a Modified Release of Recombinant Human Thyroid Stimulating Hormone [Completed]
Forty-six (46) eligible, healthy subjects who provide written informed consent will be
enrolled to participate in a 2 arm parallel group study to assess and compare the
pharmacokinetics and safety profile of Thyrogen dosed at 0. 1 mg versus a modified release
formulation of recombinant human thyroid stimulating hormone (rhTSH) dosed at 0. 1 mg. Ten
(10) of these subjects will have the thyroid uptake of radioiodine (123I) measured at
baseline and following their single dose of study medication. All doses will be administered
via intramuscular (IM) injection.
Following confirmation of study eligibility, subjects will be randomized in a 1: 1 ratio to
receive either a single administration of 0. 1 mg of Thyrogen (THYR) or 0. 1 mg of the modified
release.
Randomization will be stratified by whether or not patients will have the thyroid uptake of
radioiodine (123I) measured following their single dose of study medication. Five (5)
patients in each treatment arm will have uptake measured, while 18 in each arm will not.
Each subject will have blood samples taken to determine the pharmacokinetics of serum TSH at
- 12 hours and just prior to dosing and at various hours up to 14 days following the
administration of Thyrogen or the modified release formulation. In addition, for the
evaluation of pharmacodynamics, each subject will have samples of blood taken to determine
serum free T4, total T4, free T3, and total T3 at - 12 hours and just prior to dosing and at
various hours up to 14 days following the administration of study treatments.
All subjects will undergo a 12-lead electrocardiogram (ECG) just prior to dose administration
and 1, 2, 3, 4, 5, 7, 10 and 14 days following study treatment administration. In addition,
subjects will undergo 24 hours of Holter monitoring at baseline and four (4) consecutive
24-hour Holter monitoring sessions post treatment to yield a total of 96 hours of continuous
monitoring of cardiac function following treatment administration. All subjects will undergo
ultrasound evaluations to determine thyroid volume at baseline and 48 hours following
treatment administration.
Twenty-four hours following the administration of Thyrogen or the modified release
formulation, a subset of five (5) subjects in each treatment arm will receive a dose of 123I
prepared to be 400µCi on the day of radioiodine administration based on the utilized nuclear
pharmacy’s calibration schedule. Thyroid gland uptake will be measured via a probe in these
10 subjects at 6, 24 and 48 hours following radioiodine administration.
Blood chemistry, complete blood count (CBC), urinalysis and a physical exam will be conducted
14 days after treatment administration, or at the time of early termination, as a final
safety assessment.
Each subject’s duration of study participation will be approximately 4 weeks.
Quality of Life, Recombinant TSH (Thyrogen) and Thyroid Cancer [Recruiting]
To evaluate quality of life in patients after 10 days pause of thyroid medication
(Liothyronine) compared to treatment with recombinant TSH (Thyrogen) before radioiodine
uptake and treatment in a double-blinded, randomised cross-over design.
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