Parathyroid Transplant for Hypoparathyroidism

Overseen By Esther Lee, BScN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Karen Devon

Must be taking: Calcium, Vitamin D

Disqualifiers: Under 18, Pregnancy, Advanced cancer, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

5 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new procedure for individuals with severe hypoparathyroidism, a condition that can occur after thyroid surgery and leads to low calcium levels despite regular treatment. The trial involves transplanting parathyroid glands from a donor (known as a Donor Parathyroid Transplant) to help manage symptoms like numbness or tingling and reduce the need for high doses of calcium and vitamin D. It seeks participants who continue to struggle with these issues despite more than a year of treatment after thyroid surgery and who qualify for organ transplants. As an unphased trial, this study provides a unique opportunity for patients to access innovative treatment options not yet widely available.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. However, since the trial involves a transplant, you may need to continue certain medications like immunosuppressants. It's best to discuss this with the trial coordinators.

What prior data suggests that this parathyroid transplant procedure is safe?

Earlier studies have shown promise for parathyroid transplants as a treatment for hypoparathyroidism. Research suggests this method could be both safe and effective. The treatment involves transplanting parathyroid tissue to help restore the body's balance of calcium and other minerals.

Some patients who received parathyroid transplants experienced positive results with few side effects. These studies indicate that the procedure is generally well-tolerated. However, like any transplant, medications may be needed to prevent tissue rejection, and these medications can sometimes cause side effects.

Overall, while more research is needed, current findings support the safety of parathyroid transplants for treating hypoparathyroidism. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the parathyroid transplant for hypoparathyroidism because it introduces a completely new approach to treatment by using a donor parathyroid gland. Unlike standard treatments that rely on high doses of calcium and vitamin D supplements to manage symptoms, this transplant aims to restore natural parathyroid function. By potentially allowing the body to regulate calcium levels on its own, this method could reduce or even eliminate the need for daily supplements and frequent IV calcium infusions.

What evidence suggests that this parathyroid transplant is effective for hypoparathyroidism?

Research shows that parathyroid allotransplantation, which participants in this trial will undergo, could be a promising treatment for hypoparathyroidism. This method aims to restore normal parathyroid function, helping control calcium levels in the body. Studies have found that patients often reach normal parathyroid hormone (PTH) levels starting from the third week after the transplant. In some cases, benefits such as improved calcium balance can last for several months. This approach might be more effective for patients who haven't responded well to standard treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

Karen Devon, MD, MSc, FRCSC, FACS

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for individuals with severe hypoparathyroidism that persists after thyroid surgery and doesn't respond well to standard treatments. Participants must be struggling with symptoms despite conventional therapy.

Inclusion Criteria

My low calcium levels after thyroid surgery haven't improved with medication.

Biochemical blood test consistent with hypoparathyroidism

I have had my entire thyroid removed.

Exclusion Criteria

I have prostate cancer, lymphoma in remission, or skin cancer but am still eligible for a transplant.

My cancer cannot be treated with a transplant.

I am under 18 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-operative Assessment

Comprehensive assessment by endocrine surgery, endocrinology, and transplant team; includes baseline blood work, psychiatric evaluation, and vaccination review

1-2 weeks

1 visit (in-person)

Transplantation

Parathyroid transplantation from a neurologically deceased donor; includes surgical procedure and immediate post-operative care

1 day

Hospital admission for surgery

Immediate Post-operative Follow-up

Monitoring of calcium profile and response to treatment on days 3 and 7 post-surgery

1 week

2 visits (in-person)

Long-term Follow-up

Monitoring of calcium profile and patient symptoms at 1, 3, and 12 months post-operatively

12 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Donor Parathyroid

Trial Overview The study is testing the safety and effectiveness of transplanting parathyroid tissue from a deceased donor into patients who have not responded to other treatments for severe post-surgical hypoparathyroidism.

How Is the Trial Designed?

Group I: Parathyroid Transplant Experimental Treatment 1 Intervention

Patients with permanent refractory hypoparathyroidism after total thyroidectomy will be entered in this study to undergo parathyroid transplantation from a neurologically deceased donor. Inclusion criteria are patients who have had a prior total thyroidectomy with both biochemical hypoparathyroidism and symptomatic hypocalcemia (numbness, tingling, or other neurologic symptoms) requiring daily high dose calcium (greater than 2000 mg per day), vitamin D (greater than 2 mcg of calcitriol per day) supplementation and/or intermittent IV calcium infusion. Patients for inclusion must have failed this medical management after at least 1 year of treatment and meet standard criteria for receiving organ transplant.

Donor Parathyroid is already approved in Canada, United States for the following indications:

Approved in Canada as Parathyroid Allotransplant for:

• Severe Refractory Hypoparathyroidism

Approved in United States as Parathyroid Allotransplant for:

• Severe Refractory Hypoparathyroidism

Who Is Running the Clinical Trial?

Karen Devon

Lead Sponsor

Trials

1

Recruited

5+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Published Research Related to This Trial

Transplanting human adenomatous parathyroid cells into rabbits resulted in a significant increase in parathyroid hormone levels, indicating that these cells can function effectively after transplantation.

No signs of malignant transformation were observed in the transplanted parathyroid cells, suggesting that this method could be a safe alternative for treating permanent hypoparathyroidism in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xenotransplantation of human cryopreserved parathyroid tissue isolated from parathyroid adenomas to normocalcemic rabbits. Ayşan, E., Düzköylü, Y., Can, İ., et al.[2020]

A new parathyroid allotransplant technique was developed, showing a 70% success rate in restoring parathyroid function in 10 patients with permanent hypoparathyroidism after a mean follow-up of 12 months.

The procedure is cost-effective, requires minimal staff and equipment, and involves only short-term use of immunosuppressants, with no major complications reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parathyroid Allotransplant With a New Technique: A Prospective Clinical Trial. Aysan, E., Altug, B., Ercan, C., et al.[2017]

In a study of 57 patients who underwent total parathyroidectomy plus autotransplantation, those with hypoparathyroidism required significantly more calcium carbonate and vitamin D3 supplements than those without hypoparathyroidism, indicating a higher need for these nutrients post-surgery.

Despite the increased supplement requirements, hypoparathyroid patients did not experience any adverse side effects, and overall symptoms improved significantly within three months, with bone mineral density also increasing after one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoparathyroidism after total parathyroidectomy plus subcutaneous autotransplantation for secondary hyperparathyroidism--any side effects? Chou, FF., Chi, SY., Hsieh, KC.[2021]

Permanent hypoparathyroidism after thyroid surgery is rare, occurring in less than 1-2% of cases when performed by skilled surgeons, highlighting the importance of parathyroid identification and preservation during surgery.

Parathyroid autotransplantation, whether fresh or cryopreserved, is a viable option to prevent or manage permanent hypoparathyroidism, and cultured parathyroid cell allotransplantation may offer an alternative treatment without the need for immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parathyroid transplantation in thyroid surgery. Barczyński, M., Gołkowski, F., Nawrot, I.[2020]

In a study involving four recipients of parathyroid allotransplantation, two recipients maintained functional allografts for over four years, indicating potential long-term success of the procedure.

The study found that traditional immunological factors like HLA-matching and de novo DSA positivity did not significantly predict the success of parathyroid allotransplantation, suggesting that other factors may be more important for monitoring outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Importance of HLA typing, PRA and DSA tests for successful parathyroid allotransplantation. Yucesan, E., Goncu, B., Ozdemir, B., et al.[2020]

A 47-year-old woman with permanent hypoparathyroidism successfully underwent parathyroid allotransplantation, resulting in the cessation of her long-term intravenous calcium therapy after 3.5 years of treatment.

The transplantation was safe, with no complications reported, and led to stable serum calcium levels without the need for IV calcium, highlighting its efficacy as a cost-effective treatment option for patients with persistent hypoparathyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discharging a Patient Treated With Parathyroid Allotransplantation After Having Been Hospitalized for 3.5 Years With Permanent Hypoparathyroidism: A Case Report. Aysan, E., Yucesan, E., Idiz, UO., et al.[2020]

A survey of 252 patients with permanent hypoparathyroidism revealed that most experience severe symptoms despite standard treatments, with an average quality of life score of 5 out of 10, indicating a significant impact on their daily lives.

There is a strong interest among patients in exploring parathyroid transplantation as a treatment option, particularly a less invasive method involving intramuscular injections, although concerns about the need for immunosuppressive therapy were noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients' views about parathyroid transplantation for post-thyroidectomy hypoparathyroidism. Stevenson, A., Mihai, R.[2023]

Parathyroid glands harvested using a two-stage procurement method and stored for up to 48 hours in cold University of Wisconsin media maintained their viability and functional integrity, showing no signs of hypoxic stress or apoptosis.

The glands demonstrated preserved calcium-sensing capacity and successfully engrafted in vivo after transplantation into mice, indicating that this method is effective for ensuring the success of parathyroid allotransplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Multi-stage Procurement on the Viability and Function of Human Donor Parathyroid Glands. Kelly, YM., Ward, C., Zhang, R., et al.[2022]

In a study of 85 patients who underwent allotransplantation of cultured parathyroid cells for surgical hypoparathyroidism, 55.1% retained endocrine function for more than 2 months, suggesting that this method can be a viable treatment option for permanent hypoparathyroidism.

The study demonstrated that the survival of the parathyroid cell allografts averaged 6.35 months, and interestingly, the success of the grafts did not depend on the initial viability or secretory activity of the cultured cells used for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allotransplantation of cultured parathyroid progenitor cells without immunosuppression: clinical results. Nawrot, I., Woźniewicz, B., Tołłoczko, T., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8953572/

Parathyroid Allotransplantation: A Systematic Review - PMC Parathyroid allotransplantation by design is a one-time cure through its restoration of the parathyroid function and, therefore, could be the solution.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002961021004050

Parathyroid allotransplantation for the treatment of ... Parathyroid allotransplantation presents a potentially safe and effective therapeutic option for the definitive treatment of permanent hypoparathyroidism.

3. bmcsurg.biomedcentral.com bmcsurg.biomedcentral.com/articles/10.1186/s12893-016-0165-y

Living-donor parathyroid allotransplantation for therapy ... Initial results were encouraging showing normal PTH levels from the third week after transplantation [22] or graft survival up to 8 months [23].

4. jes-online.org jes-online.org/pdf/10.16956/jes.2025.25.1.1

Advancements and Clinical Strategies in Parathyroid ... Parathyroid transplantation holds significant promise as a treatment for hypoparathyroidism. Further research and clinical trials are warranted ...

5. journals.lww.com journals.lww.com/transplantationdirect/fulltext/2022/04000/procurement_of_deceased_donor_parathyroid_glands.1.aspx

Procurement of Deceased Donor Parathyroid Glands With ... Parathyroid allotransplantation is a burgeoning treatment for severe hypoparathyroidism. Deceased donor parathyroid gland (PTG) procurement can be ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06961071

NCT06961071 | Parathyroid Allotransplant for Treatment of ... This study is being done to see if transplanting parathyroid tissue into the forearm will help hypo-parathyroid patients achieve parathyroid hormone (PTH) ...

7. gs.amegroups.org gs.amegroups.org/article/view/17084/html

Short and long-term impact of parathyroid ... - Gland Surgery This review aims to define the role and impact of parathyroid autotransplantation undertaken during total thyroidectomy.