Imaging Dye for Parathyroid Disease

Overseen By Azeem Izhar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Alabama at Birmingham

Disqualifiers: Iodine allergy, Shellfish allergy, Pregnancy

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

417 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special imaging dye called indocyanine green (ICG) to determine if it can make thyroid and parathyroid surgeries safer and more accurate. The researchers aim to find out if this dye can help doctors identify and preserve the parathyroid glands during surgery. Suitable candidates for this trial include those needing surgery for parathyroid issues and who do not have allergies to iodine, shellfish, or indocyanine green. As a Phase 4 trial, this research focuses on understanding how this FDA-approved and effective treatment can benefit more patients.

Do I need to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What is the safety track record for Indocyanine Green?

Research has shown that indocyanine green (ICG) is generally safe for use in thyroid and parathyroid gland surgeries. In past studies, ICG helped doctors locate and protect the parathyroid glands during surgery, reducing the risk of complications like hypoparathyroidism, a condition where the body produces insufficient parathyroid hormone.

Some studies have used ICG in surgeries such as thyroid removal and found it beneficial. However, limited information exists on how much it improves surgical outcomes. Although no major safety issues have been reported, its limited use in parathyroid surgeries suggests that more research is needed to fully understand its benefits and risks.

This study is in Phase 4, indicating that ICG has already been approved for other uses, which supports its safety profile. Phase 4 trials typically focus on gathering more information about a treatment after approval, so any risks are likely well understood. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard procedures for identifying parathyroid glands during surgery, which often rely on the surgeon’s experience and visual cues, Indocyanine Green (ICG) offers a unique advantage by providing real-time imaging. This dye is administered intravenously and fluoresces under near-infrared light, allowing surgeons to accurately identify and preserve parathyroid glands, reducing the risk of accidental damage. Researchers are excited about ICG because it can improve surgical outcomes and patient safety by ensuring more precise gland identification, potentially reducing surgery time and complications.

What evidence suggests that this imaging dye is effective for parathyroid disease?

Research has shown that Indocyanine Green (ICG), which participants in this trial may receive, can be useful in parathyroid surgery. One study found that ICG helped surgeons locate parathyroid glands in about 88% of cases, enhancing the safety and precision of surgeries. Other studies have also demonstrated that ICG improves the accuracy of parathyroidectomy, the removal of parathyroid glands. This makes ICG a promising option for individuals requiring surgery for parathyroid disease. ^{5 6 7 8 9}

Who Is on the Research Team?

Herbert Chen, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults over 18 who need thyroid or parathyroid surgery. It's not suitable for those with allergies to iodine, shellfish, or indocyanine green, nor for pregnant individuals.

Inclusion Criteria

I am over 18 years old.

Exclusion Criteria

Patients with allergy to indocyanine green

Pregnancy

Patients with iodine or shellfish allergies would be excluded

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo thyroidectomy or parathyroidectomy with the administration of indocyanine green and use of fluorescence imaging

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery, focusing on postoperative hypocalcemia and other complications

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Indocyanine Green

Trial Overview The study tests if using a special dye called indocyanine green and a portable imaging device can help surgeons better identify and protect the parathyroid glands during surgery.

How Is the Trial Designed?

Group I: Parathyroid patients Experimental Treatment 2 Interventions

patients who require parathyroid identification and preservation during parathyroid surgery maneuver

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Stryker Nordic

Industry Sponsor

Trials

35

Recruited

4,400+

Published Research Related to This Trial

Intravenous contrast agents, used in imaging procedures like MRI and CT scans, have a low incidence of adverse events, but clinicians must be prepared to manage reactions effectively.

The review highlights various potential adverse events associated with iodinated and gadolinium-based contrast agents, including allergic reactions and nephrotoxicity, emphasizing the importance of risk assessment and premedication strategies for at-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Imaging Contrast Media Complications: The Basics That Every Clinician Needs to Know. Rose, TA., Choi, JW.[2022]

In a study comparing patients with primary hyperparathyroidism to those with normal parathyroid glands, indocyanine green (ICG) fluorescence was significantly more intense in the abnormal parathyroid tissue, indicating its potential for aiding in surgical identification.

The study found that the fluorescence intensity of diseased parathyroid (4 ± 2) was notably higher than that of normal parathyroid (2 ± 1) and thyroid tissue (3 ± 1), suggesting that ICG/NIR technology could be a valuable tool during parathyroid surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Indocyanine Green and Fluorescence Angiography in Parathyroid Surgery: A Feasibility Study. Maser, C., Kohlbrenner, AH., Dirks, R.[2021]

Gadoxetic acid, a gadolinium-based contrast agent, showed a low incidence of hypersensitivity reactions (0.3%) in 14,850 administrations, with no reported deaths, indicating a favorable safety profile.

The risk of nephrogenic systemic fibrosis (NSF) in patients with severe kidney impairment remains uncertain, with an upper bound estimate of 2.8% based on limited data, suggesting more research is needed to fully understand this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events to the Gadolinium-based Contrast Agent Gadoxetic Acid: Systematic Review and Meta-Analysis. Schieda, N., van der Pol, CB., Walker, D., et al.[2020]

Indocyanine green (ICG) fluorescence has a high sensitivity of 93.8% for identifying parathyroid glands during surgery, making it a reliable tool for surgeons.

The use of ICG not only helps in identifying the glands but also predicts postoperative function effectively, with a diagnostic odds ratio of 54.57, indicating a strong correlation between ICG scores and the risk of postoperative hypoparathyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indocyanine green fluorescence for parathyroid gland identification and function prediction: Systematic review and meta-analysis. Kim, DH., Kim, SH., Jung, J., et al.[2022]

Indocyanine green (ICG) NIR fluorescent imaging effectively visualized the parathyroid glands in a study involving three dogs, suggesting its potential utility in surgical procedures like thyroidectomies.

The optimal dose for ICG was estimated to be 18.75 µg/kg, with fluorescence detectable for about 106.7 seconds post-injection, indicating that ICG can help surgeons identify parathyroid glands during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indocyanine green as a near-infrared fluorescent agent for identifying parathyroid glands during thyroid surgery in dogs. Suh, YJ., Choi, JY., Chai, YJ., et al.[2019]

Indocyanine green (ICG) fluorescence imaging was successfully used in three patients undergoing reoperative neck surgery for primary hyperparathyroidism, allowing for accurate identification and removal of parathyroid glands.

The use of ICG helped distinguish parathyroid glands from surrounding soft tissue, suggesting its potential as a valuable tool for intraoperative guidance in parathyroid surgeries, although further studies are needed for first-time surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of Indocyanine Green Fluorescence Imaging for Intraoperative Localization in Reoperative Parathyroid Surgery. Sound, S., Okoh, A., Yigitbas, H., et al.[2022]

In a study of 66 patients undergoing parathyroidectomy, fluorescence angiography using indocyanine green (ICG) dye demonstrated a rapid average time to peak fluorescence of 38.0 seconds, indicating its effectiveness for real-time identification of parathyroid adenomas.

The in-situ fluorescence rate was high at 97%, suggesting that ICG FA is a reliable tool during surgery, especially when compared to traditional imaging methods, which had lower detection rates for adenomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid intraoperative perfusion assessment of parathyroid adenomas with ICG using a wide-field portable hand-held fluorescence imaging system. Matson, J., Lwin, TM., Bouvet, M.[2022]

Indocyanine green (ICG) near-infrared fluorescent imaging was effective in localizing parathyroid glands during surgery for primary hyperparathyroidism, with 92.9% of identified glands showing ICG uptake in a study of 33 patients.

All patients achieved a biochemical cure after surgery, and there were no cases of postoperative hypoparathyroidism among those who underwent subtotal parathyroidectomy, indicating the safety of ICG use in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The utility of indocyanine green near infrared fluorescent imaging in the identification of parathyroid glands during surgery for primary hyperparathyroidism. Zaidi, N., Bucak, E., Okoh, A., et al.[2017]

Gadolinium-based contrast agents are generally very safe, with a low incidence of immediate adverse events reported over the past 10 years, particularly in abdominal MRI procedures, which had the highest rate of 0.013%.

Among the different agents, gadobenate dimeglumine was associated with more severe reactions, including fatalities, suggesting that nonionic linear agents and gadopentetate dimeglumine may have a better safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of immediate gadolinium contrast media reactions. Prince, MR., Zhang, H., Zou, Z., et al.[2022]

In a study of 32,659 MRI administrations, the overall rate of acute adverse reactions to gadolinium-based contrast agents was low at 0.16%, with 51 reactions reported among 50 patients.

Gadopentetate dimeglumine had a slightly lower adverse reaction rate (0.14%) compared to gadobenate dimeglumine (0.28%), with most reactions being mild, although two severe reactions were associated with gadobenate dimeglumine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute adverse reactions to gadopentetate dimeglumine and gadobenate dimeglumine: experience with 32,659 injections. Abujudeh, HH., Kosaraju, VK., Kaewlai, R.[2022]

Indocyanine green (ICG) enhanced fluorescence imaging is a promising technique for real-time intraoperative imaging, particularly in endocrine surgeries related to the parathyroid glands.

Current literature shows variability in the use of ICG regarding doses and techniques, indicating a need for standardized protocols to optimize its effectiveness in preserving parathyroid function during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of ICG enhanced fluorescence for the evaluation of parathyroid gland preservation. Jitpratoom, P., Anuwong, A.[2020]

Gadolinium-based MRI contrast agents, once thought safe, have been linked to serious complications like acute renal failure and nephrogenic systemic fibrosis in patients with end-stage renal disease (ESRD), leading to restrictions on their use in these high-risk groups.

The editorial emphasizes the need for careful monitoring and documentation of adverse events related to Gad-CAs, as well as collaboration among medical professionals to manage and mitigate risks associated with their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Good MRI images: to Gad or not to Gad? Steen, H., Schwenger, V.[2019]

Near-infrared fluorescence imaging using indocyanine green (ICG) is a feasible and safe method for identifying parathyroid glands during thyroid surgery, with added value in confirming their presence in over half of the surgeries performed.

The study involved 30 operations in 26 patients, and no intraoperative or postoperative complications were reported due to the use of ICG, highlighting its safety in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of indocyanine green fluorescence imaging for intraoperative identification of parathyroid glands during thyroid surgery. van den Bos, J., van Kooten, L., Engelen, SME., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12185159/

Identifying and Preserving Parathyroid Glands During Thyroid ... Our findings showed that ICG successfully helped surgeons locate parathyroid glands in an average of 88.25% of cases. Conclusion. Our research ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0039606025004751

Combined near-infrared autofluorescence and ... This was a single-institution controlled trial examining whether the intraoperative combination of near-infrared-induced autofluorescence of the parathyroid ...

3. link.springer.com link.springer.com/article/10.1007/s00405-025-09679-0

Indocyanine green fluorescence in parathyroidectomy This study highlights the potential benefits of ICG NIR fluorescence endoscopy in improving the efficiency and precision of parathyroidectomy.

4. gs.amegroups.org gs.amegroups.org/article/view/16526/html

The use of ICG enhanced fluorescence for the evaluation of ... This study reviews the current status of ICG enhanced fluorescence imaging and parathyroid preservation in both thyroid and parathyroid surgery.

5. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1193900/full

Indocyanine green angiography-guided thyroidectomy ... We propose a randomized single-blind controlled and multicenter clinical trial to assess the efficacy and safety of ICG angiography-guided thyroidectomy.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5676163/

The use of ICG enhanced fluorescence for the evaluation of ... This technique is used to reduce the chances of hypoparathyroidism after a patient undergoes thyroid surgery and can help to preserve postoperative parathyroid ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8468084/

Indocyanine Green Angiography for Parathyroid Gland ... ICG angiography is a feasible adjunct procedure for parathyroid identification and postoperative functional prediction in transoral endoscopic thyroidectomy.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0011384024002314

Determination of parathyroid function after total ... Use of fluorescence imaging and indocyanine green during thyroid and parathyroid surgery: results of an intercontinental Delphi survey. Surgery, 172 (6S) ...

9. nature.com nature.com/articles/s41598-017-08347-6

Intraoperative Parathyroid Localization with Near-Infrared ... However, the toxicity and lack of data demonstrating the improvement of outcomes have restricted its popularization in parathyroid surgery. Thus ...