Effect of Lithium Carbonate on Low-Dose Radioiodine Therapy in Early Thyroid Cancer

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00251316
• Collaborator: (none)
• Enrollment: 34
• Location: 1
• Arms: 2
• Duration (Months): 73
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study will examine the safety and effectiveness of using lithium, which has been used to enhance the effectiveness of high-dose 131I, with a single low dose (30 mCi) of 131I for thyroid ablation in patients with recently diagnosed papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid.

Participants are randomly assigned to receive lithium capsules or placebo (look-alike capsules with no active ingredient). They follow a low-iodine diet for 2 weeks before starting treatment and are then admitted to the NIH Clinical Center for study and treatment for 11 days, during which they remain on the low-iodine diet. Blood samples are collected almost every day to analyze thyroid hormones, kidney and liver function, lithium concentrations and other tests.

Condition or Disease	Intervention/Treatment	Phase
Thyroid Cancer; Differentiated Thyroid Carcinoma	Drug: Lithium Carbonate; Drug: Placebo	Phase 2

Detailed Description

Postsurgical thyroid remnant ablation with (131)I is considered standard clinical care for most cases of papillary and follicular thyroid cancer, to eliminate normal thyroid tissue which may contain microscopic cancer. Furthermore, ablation enhances the sensitivity of subsequent (131)I scanning and serum thyroglobulin (TG) measurement for the detection of recurrent or persistent disease. Low dose (131)I (30 mCi) successfully ablates thyroid remnant in 8-61% of cases. This dose can be repeated and result in overall less radiation exposure than that associated with high dose therapy (100 mCi). Ablation achieved with one or more small doses of radioactive iodine is not associated with decreased survival or cancer recurrence. According to the literature there is no difference in the 30-year recurrence rates between groups receiving low and high dose ablation therapy for well differentiated thyroid cancer without distant metastases at the time of initial therapy. The benefits of using low dose of (131)I are minimization of whole body radiation exposure, reduction in side effects and lower cost. Higher rates of successful ablation by low dose of 131I could be achieved by increasing uptake of (131)I and/or lengthening retention of radioiodine in the remnant thyroid tissue. Recombinant human thyroid-stimulating hormone (rhTSH) has been used successfully to increase radioiodine uptake. Lithium has been used to increase radioiodine retention and has been shown to be useful in the treatment of residual or metastatic cancer. The combination of rhTSH and lithium as adjuncts to 30 mCi radioactive iodine (RAI) ablation therapy in low risk thyroid cancer patients may provide a method that reduces the cumulative dose of radioiodine needed to successfully treat thyroid cancer. The specific aim of this study is to determine whether adjunct lithium carbonate improves the success rate of postsurgical ablation of thyroid remnants using low dose (131)I (30 mCi) and rhTSH in low risk patients with differentiated thyroid carcinoma. Patients with well-differentiated papillary or follicular thyroid cancer stage I or II, according to the National Thyroid Cancer Treatment Cooperative Study (NTCTCS) classification at time of surgery, will be enrolled. Eligible patients will have had a total or near-total thyroidectomy within 6 months of enrollment. This randomized, placebocontrolled, double-blind study will permit an evaluation of the risk/benefit ratio of adding lithium as an adjuvant to the already established method of administering low-dose (131)I ablation therapy, to optimize the (131)I retention. All patients will undergo diagnostic rhTSH (123)I whole body scan at the end of the study to assess the success of thyroid ablation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effects of Lithium Carbonate on Low Dose Radioiodine Ablation in Early Thyroid Cancer Treatment
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lithium Carbonate Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive lithium capsules.	Drug: Lithium Carbonate; 30 mCi of 131I; Other Names: Lithium carabonate
Placebo Comparator: Placebo Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive placebo (look-alike capsules with no active ingredient).	Drug: Placebo; Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive placebo (look-alike capsules with no active ingredient).; Other Names: Identical placebo

Outcome Measures

Primary Outcome Measures

1. The Rate of Successful Thyroid Ablation as Defined by Negative Recombinant Human Thyrotropin (rhTSH) Stimulated Radioiodine Whole Body Scan (RAI WBS) at 1 Year. [1 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA

1. Patients older than 16 years with well-differentiated papillary or follicular thyroid cancer stage I or II, according to the NTCTCS classification at time of surgery

2. Patients younger than 45 years with any size of primary papillary or follicular tumor

3. Patients older than 45 years with:

4. primary papillary tumor less than 4 cm or

5. primary follicular tumor less than 1 cm

• EXCLUSION CRITERIA

1. Patients with postsurgical thyroid remnant more than 5 g

2. Patients with distant metastases

3. Patients above 45 years of age having:

4. known cervical lymph nodes metastases

5. microscopic multifocal follicular cancer

6. microscopic extraglandular invasion of follicular cancer

7. gross extraglandular invasion of papillary or follicular cancer

8. Patients with confirmed histological subtypes of well-differentiated thyroid cancer such as Hurtle cell carcinoma, insular and tall cell variants of papillary cancer.

9. Pregnant or lactating women

10. Patients with renal impairment defined as repeat serum creatinine concentrations above 1.5 mg/dl on thyroid hormone

11. Patients on chronic lithium therapy for psychiatric illness

12. Patients with current unstable cardiovascular conditions

13. Patients with severe chronic medical conditions (liver failure, severe debilitation, dehydration, sodium depletion, any other cancer requiring therapy, etc)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Monica C Skarulis, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994 Nov;97(5):418-28. Erratum in: Am J Med 1995 Feb;98(2):215.
• Mazzaferri EL. An overview of the management of papillary and follicular thyroid carcinoma. Thyroid. 1999 May;9(5):421-7. Review.
• Sherman SI. Thyroid carcinoma. Lancet. 2003 Feb 8;361(9356):501-11. Review.

• Responsible Party: Monica Skarulis, MD, PI, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00251316
• Other Study ID Numbers: 060025; 06-DK-0025
• First Posted: Nov 9, 2005
• Last Update Posted: Feb 4, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by Monica Skarulis, MD, PI, National Institutes of Health Clinical Center (CC): Thyroid Neoplasm; I-131; Radiation Dose; Radiation Effect; Pharmaceutical Adjuvant; Thyroid Cancer
• Additional relevant MeSH terms: Thyroid Neoplasms; Thyroid Diseases; Lithium Carbonate

Study Results

Participant Flow

Recruitment Details	87 patients were screened for the eligibility for this study. Total of 34 patients were enrolled into the study
Pre-assignment Detail	The sample size for the trial is 100 patients and the goal for the number of patients to be randomized by November 2010 is 74 patients.

Arm/Group Title	Lithium Carbonate	Placebo
Arm/Group Description	Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive lithium capsules.	Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive placebo (look-alike capsules with no active ingredient).
Period Title: Overall Study
STARTED	17	17
COMPLETED	15	14
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Lithium Carbonate	Placebo	Total
Arm/Group Description	Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive lithium capsules.	Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive placebo (look-alike capsules with no active ingredient).	Total of all reporting groups
Overall Participants	15	14	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.8 (11.8)	38.6 (10.2)	39.2 (10.9)
Sex: Female, Male (Count of Participants)
Female	12 80%	12 85.7%	24 82.8%
Male	3 20%	2 14.3%	5 17.2%
Race/Ethnicity, Customized (Number) [Number]
African American	1 6.7%	1 7.1%	2 6.9%
Caucasian	12 80%	13 92.9%	25 86.2%
Hispanic	2 13.3%	0 0%	2 6.9%
Region of Enrollment (participants) [Number]
United States	15 100%	14 100%	29 100%

Outcome Measures

1. Primary Outcome

Title	The Rate of Successful Thyroid Ablation as Defined by Negative Recombinant Human Thyrotropin (rhTSH) Stimulated Radioiodine Whole Body Scan (RAI WBS) at 1 Year.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lithium Carbonate	Placebo
Arm/Group Description	Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive lithium capsules.	Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive placebo (look-alike capsules with no active ingredient).
Measure Participants	15	14
Number [Participants]	10 66.7%	10 71.4%

Adverse Events

Arm/Group Title	Lithium Carbonate		Placebo
Arm/Group Description	Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive lithium capsules.		Patients recently diagnosed with papillary or follicular thyroid cancer who have had their thyroid gland removed and whose cancer has not spread beyond the thyroid may be eligible for this study. Participants in this arm receive placebo (look-alike capsules with no active ingredient).
All Cause Mortality
	Lithium Carbonate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lithium Carbonate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress	0/15 (0%)	0	1/14 (7.1%)	1
Other (Not Including Serious) Adverse Events
	Lithium Carbonate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.