ThyroidPhase 2NCT03109847

Metformin to Mitigate Sequelae of Radioactive Iodine Treatment for Thyroid Cancers

A Phase 2 study testing Metformin Hydrochloride and Radioactive Iodine in people with Thyroid, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This pilot clinical trial studies how will metformin hydrochloride works in mitigating the side effects of radioactive iodine treatment in patients with differentiated thyroid cancer. Metformin hydrochloride may reduce the metabolic activity of cancer cell and of surrounding supportive tissues. Read more about this study

Who is it for?: Ages 18 to 90 years
Conditions the study is for: Thyroid
What is being tested?: Metformin Hydrochloride and Radioactive Iodine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 13 participants
Where: 1 siteUnited States
Study dates: 5 Jan 2017to 7 Dec 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 90 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects with a diagnosis of differentiated thyroid cancer who have undergone total or near-total thyroidectomy and are candidates for iodine I-131 (I-131) treatment at Thomas Jefferson University Hospital (TJUH) are eligible to participate
Subjects must be diagnosed with differentiated thyroid cancer
Patients must have previously undergone or plan to undergo thyroidectomy; for those patients who have previously undergone surgery, pre-operative labs, including complete blood cell count with differential must be available
Patients who have a negative urine pregnancy test prior to enrollment. This should be done as part of pre-admission testing prior to surgery (within 14 days of study enrollment).
All subjects must be able to comprehend and sign a written informed consent document

Who cannot join

Subjects who are pregnant or may become pregnant during metformin administration in accordance with radioactive iodine treatment guidelines
Subjects on metformin for any reason during the preceding 4 weeks
Diabetic subjects are eligible if they are not taking metformin, insulin or sulfonylureas
Subjects who have received iodinated contrast dye. Metformin treatment can be started the day after subjects complete iodinated contrast treatment. If a CT scan with contrast is scheduled after screening and consent, the metformin treatment should be stopped the day before iodinated contrast administration. Metformin can be resumed on the day after last iodinated contrast was administered to the subject.
Patients with history of hepatic dysfunction or hepatic disease and abnormal liver function tests (previously documented alanine aminotransferase greater than 40 IU/dL and/or plasma aspartate aminotransferase greater than 45 IU/d); patients who have a history of hepatic dysfunction or hepatic disease but whose most recent liver function tests have been documented as normal will be eligible to participate
Patients with plasma creatinine level greater than 1.3 mg/dL

Show all 16Show fewer

Patients with plasma alkaline phosphatase greater than 190 IU/dL
Patients with plasma bicarbonate less than 22 mEq/L or history of lactic or any other metabolic acidosis
Patients with history of congestive heart failure
Patients with myocardial ischemia or peripheral muscle ischemia
Patients with sepsis or severe infection
Patients with history of lung disease currently requiring any pharmacologic or supplemental oxygen treatment
Patients with a current history (in the past 30 days) of heavy drinking which is defined in accordance with CDC definition as more than 8 drinks per week for women and more than 15 drinks per week for men. A standard drink contains .6 ounces of pure alcohol. Generally, this amount of pure alcohol is found in 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a "shot" of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey). While on study, patients should limit their alcohol consumption to no more than 8 drinks per week for women and no more than 15 drinks per week for men. Patients who feel they cannot comply with this recommendation are not eligible.
Patients with a systemic disease that could affect their bone marrow or peripheral blood cells (e.g. systemic lupus erythematosus, human immunodeficiency virus infection, rheumatoid arthritis)
Patients who have received or will receive medication that could affect their hematologic state (tyrosine kinase inhibitors, cytotoxic chemotherapy)
Patients who are Non-English speaking *Note: This is due to the nature of the study and the process for full translations of the study documents.

Trial locations and contacts

1 site in 1 country.

United States1 site

Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: Pilot Study of Metformin to Mitigate Sequelae of Radioactive Iodine Treatment for Well-Differentiated Thyroid Cancers

Read the detailed description

PRIMARY OBJECTIVES:

To evaluate if treatment with metformin hydrochloride (metformin) inhibits radioactive iodine (RAI)-induced myelosuppression and induces faster recovery of white blood cell count to baseline values, the blood counts will be compared in the pre- and post-treatment samples.

SECONDARY OBJECTIVES:

Assess safety and tolerability of metformin treatment in subjects undergoing RAI treatment for differentiated thyroid cancer.

II. To assess the effect of metformin treatment on symptoms of xerostomia, xerophthalmia and dysgeusia as assessed by the Xerostomia Questionnaire (XQ), the modified Vanderbilt Head and Neck Cancer Symposium Survey (version 2.0), University of Washington Quality of Life Questionnaire, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTCQLQ)-Head and Neck (H\&N)35.

Conditions: Thyroid
Being tested: Metformin Hydrochloride, Radioactive Iodine, Placebo
Medical subject headings: Thyroid Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Metformin HydrochlorideDrug
Also called 1,1-Dimethylbiguanide Hydrochloride, 1115-70-4, 91485, Cidophage
Given Orally
Radioactive IodineOther
Undergo radioactive iodine treatment
PlaceboOther
Given orally

Study groups in NCT03109847
Study group	Role	What they receive
Arm I (metformin hydrochloride)	Experimental	Patients receive metformin hydrochloride PO daily for 3 days and then PO BID for up to 2 weeks after completing radioactive iodine treatment. Receives: Drug: Metformin Hydrochloride; Other: Radioactive Iodine
Arm II (placebo)	Placebo comparator	Patients receive placebo PO daily for 3 days and then PO BID for up to 2 weeks after completing radioactive iodine treatment Receives: Other: Radioactive Iodine; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Red Blood Cell Count From Pre-Resection to Post-Resection
Change in red blood cell count measured from baseline to two weeks after completion of RAI, measured via standard CBC laboratory testing. Longitudinal measures of CBC will be modeled using mixed effects linear regression. Will use a linear contrast to test the null hypothesis that change from pre-resection to post-resection is the same in the control and metformin groups.
Measured: Up to 36 months of study duration, an average of 1.5 months
Serum and Salivary Exosome Profile
Will be modeled using mixed effects linear regression
Measured: Up to 36 months of study duration
Number of Adverse Events
Number of adverse events assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version v 4.0, from treatment initiation through 15 days post-treatment follow-up.
Measured: Up to 36 months of study duration, an average of 1.5 months

Secondary outcomes (3)

Xerostomia Assessed by Modified Vanderbilt Head and Neck Cancer Symposium Survey (Version 2.0)
Measured: Up to 36 months of study duration
Xerophthalmia Assessed by Modified Vanderbilt Head and Neck Cancer Symposium Survey (Version 2.0)
Measured: Up to 36 months of study duration
Dysgeusia Assessed by Modified Vanderbilt Head and Neck Cancer Symposium Survey (Version 2.0)
Measured: Up to 36 months of study duration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Jan 20177 Dec 2022

First posted12 Apr 2017
Study start5 Jan 2017
Primary completion29 Dec 2020
Study completion7 Dec 2022

Why it stopped: Poor accrual

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for ThyroidStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Care provider
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03109847
Sponsor's protocol ID: 16D.564
Other IDs: JT 9411
Status last verified: Nov 2025
First submitted: 6 Mar 2017
Last updated: 11 Dec 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Thyroid trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot Study of Metformin to Mitigate Sequelae of Radioactive Iodine Treatment for Well-Differentiated Thyroid Cancers
ClinicalTrials.gov ID: NCT03109847
Acronym / sponsor ID: 16D.564
Conditions: Thyroid
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Poor accrual
Enrolment: 13 participants (actual)
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson UniversityUniversity, hospital or other
Study start: 5 Jan 2017 (actual)
Primary completion: 29 Dec 2020 (actual)
Study completion: 7 Dec 2022 (actual)
First posted: 12 Apr 2017 (actual)
Results: Posted 11 Dec 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

To evaluate if treatment with metformin hydrochloride (metformin) inhibits radioactive iodine (RAI)-induced myelosuppression and induces faster recovery of white blood cell count to baseline values, the blood counts will be compared in the pre- and post-treatment samples.

SECONDARY OBJECTIVES:

Assess safety and tolerability of metformin treatment in subjects undergoing RAI treatment for differentiated thyroid cancer.

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, care provider)
Number of arms: 2

Arm	Type	Receives
Arm I (metformin hydrochloride)	Experimental	Drug: Metformin Hydrochloride, Other: Radioactive IodinePatients receive metformin hydrochloride PO daily for 3 days and then PO BID for up to 2 weeks after completing radioactive iodine treatment.
Arm II (placebo)	Placebo comparator	Other: Radioactive Iodine, Other: PlaceboPatients receive placebo PO daily for 3 days and then PO BID for up to 2 weeks after completing radioactive iodine treatment

Who may qualify

Ages: 18 to 90 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Subjects with a diagnosis of differentiated thyroid cancer who have undergone total or near-total thyroidectomy and are candidates for iodine I-131 (I-131) treatment at Thomas Jefferson University Hospital (TJUH) are eligible to participate
Subjects must be diagnosed with differentiated thyroid cancer
Patients must have previously undergone or plan to undergo thyroidectomy; for those patients who have previously undergone surgery, pre-operative labs, including complete blood cell count with differential must be available
Patients who have a negative urine pregnancy test prior to enrollment. This should be done as part of pre-admission testing prior to surgery (within 14 days of study enrollment).
All subjects must be able to comprehend and sign a written informed consent document

Key exclusion criteria (16 listed)

Subjects who are pregnant or may become pregnant during metformin administration in accordance with radioactive iodine treatment guidelines
Subjects on metformin for any reason during the preceding 4 weeks
Diabetic subjects are eligible if they are not taking metformin, insulin or sulfonylureas
Subjects who have received iodinated contrast dye. Metformin treatment can be started the day after subjects complete iodinated contrast treatment. If a CT scan with contrast is scheduled after screening and consent, the metformin treatment should be stopped the day before iodinated contrast administration. Metformin can be resumed on the day after last iodinated contrast was administered to the subject.
Patients with history of hepatic dysfunction or hepatic disease and abnormal liver function tests (previously documented alanine aminotransferase greater than 40 IU/dL and/or plasma aspartate aminotransferase greater than 45 IU/d); patients who have a history of hepatic dysfunction or hepatic disease but whose most recent liver function tests have been documented as normal will be eligible to participate

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Metformin HydrochlorideAlso: 1,1-Dimethylbiguanide Hydrochloride, 1115-70-4, 91485, CidophageGiven Orally	Drug	Arm I (metformin hydrochloride)
Radioactive IodineUndergo radioactive iodine treatment	Other	Arm I (metformin hydrochloride), Arm II (placebo)
PlaceboGiven orally	Other	Arm II (placebo)

Primary outcome

Change in Red Blood Cell Count From Pre-Resection to Post-Resection
Time frame: Up to 36 months of study duration, an average of 1.5 months
Change in red blood cell count measured from baseline to two weeks after completion of RAI, measured via standard CBC laboratory testing. Longitudinal measures of CBC will be modeled using mixed effects linear regression. Will use a linear contrast to test the null hypothesis that change from pre-resection to post-resection is the same in the control and metformin groups.
Serum and Salivary Exosome Profile
Time frame: Up to 36 months of study duration
Will be modeled using mixed effects linear regression
Number of Adverse Events
Time frame: Up to 36 months of study duration, an average of 1.5 months
Number of adverse events assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version v 4.0, from treatment initiation through 15 days post-treatment follow-up.

3 secondary outcomes

Xerostomia Assessed by Modified Vanderbilt Head and Neck Cancer Symposium Survey (Version 2.0)
Time frame: Up to 36 months of study duration
Xerophthalmia Assessed by Modified Vanderbilt Head and Neck Cancer Symposium Survey (Version 2.0)
Time frame: Up to 36 months of study duration
Dysgeusia Assessed by Modified Vanderbilt Head and Neck Cancer Symposium Survey (Version 2.0)
Time frame: Up to 36 months of study duration

Results and safety

Results posted to the registry on 11 Dec 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm I (metformin hydrochloride)	6	5
Arm II (placebo)	7	7

Primary outcome: Change in Red Blood Cell Count From Pre-Resection to Post-Resection

Time frame: Up to 36 months of study duration, an average of 1.5 months. Mean (95% Confidence Interval). Unit: million cells per microliter

Measure	Arm I (metformin hydrochloride) n = 4	Arm II (placebo) n = 3
Value	-0.11 (-0.74 to 0.51)	-0.63 (-2.70 to 1.45)

Arm I (metformin hydrochloride) vs Arm II (placebo): Mean Difference (Net): 0.52 (95% CI -1.26 to 2.29), p = 0.404, t-test, 2 sided

Population analysed: Participants with both pre- and post-treatment CBC values were included in the analysis. Due to missing laboratory data, 4 participants in Arm 1 (Metformin) and 3 participants in Arm 2 (Placebo) were analyzable for this outcome.

Primary outcome: Serum and Salivary Exosome Profile

Time frame: Up to 36 months of study duration

Population analysed: The study terminated early due to poor accrual; no samples collected for exosome profiling. Therefore, no participants were analyzed for this outcome. Data were not collected and the outcome cannot be reported.

Primary outcome: Number of Adverse Events

Time frame: Up to 36 months of study duration, an average of 1.5 months. Number. Unit: Adverse Events

Measure	Arm I (metformin hydrochloride) n = 5	Arm II (placebo) n = 6
Value	32	11

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 15 days following the last administration of study treatment, an average of 1.5 months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm I (metformin hydrochloride)	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Arm II (placebo)	0 of 7 (0%)	4 of 7 (57.1%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Sidney Kimmel Cancer CenterLink provided by the sponsor.
Thomas Jefferson University HospitalLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Joseph Curry, MD principal investigator

Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Red Blood Cell Count From Pre-Resection to Post-Resection (time frame: Up to 36 months of study duration, an average of 1.5 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03109847.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2025.