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

Trial Summary

What is the purpose of this trial?

Hypoparathyroidism following thyroid surgery presents significant challenges, often leading to debilitating symptoms and reduced quality of life despite conventional treatment. Having now reported the first successful case of a deceased donor fresh tissue parathyroid allotransplant with immunosuppression in a transplant-naive recipient, the purpose of this study is to further assess the safety and efficacy of this procedure in patients with severe intractable post-surgical hypoparathyroidism.

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 data supports the effectiveness of the treatment Parathyroid Transplant for Hypoparathyroidism?

Research shows that parathyroid allotransplantation can be effective for treating permanent hypoparathyroidism, with some patients maintaining functional transplants for several years. In a study, two out of four recipients had functional transplants for more than four years, indicating potential long-term benefits. ^{1 2 3 4 5}

Is parathyroid transplantation safe for humans?

The available research does not provide specific safety data for parathyroid transplantation in humans, but it is described as a new treatment option for hypoparathyroidism. ^{3 5 6 7 8}

How is parathyroid allotransplantation different from other treatments for hypoparathyroidism?

Parathyroid allotransplantation is unique because it involves transplanting parathyroid glands from a donor to a patient with permanent hypoparathyroidism, offering a potential alternative to lifelong calcium and vitamin D supplementation. This treatment is complex, requiring specialized staff and equipment, and is considered when other options, like autotransplantation or cryopreserved tissue, are not available. ^{1 3 5 7 9}

Research Team

Karen Devon, MD, MSc, FRCSC, FACS

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

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]

References

1. United States 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. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Importance of HLA typing, PRA and DSA tests for successful parathyroid allotransplantation. [2020]

3. Turkey pubmed.ncbi.nlm.nih.gov

Xenotransplantation of human cryopreserved parathyroid tissue isolated from parathyroid adenomas to normocalcemic rabbits. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Allotransplantation of cultured parathyroid progenitor cells without immunosuppression: clinical results. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of Multi-stage Procurement on the Viability and Function of Human Donor Parathyroid Glands. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Hypoparathyroidism after total parathyroidectomy plus subcutaneous autotransplantation for secondary hyperparathyroidism--any side effects? [2021]

7. Turkey pubmed.ncbi.nlm.nih.gov

Parathyroid Allotransplant With a New Technique: A Prospective Clinical Trial. [2017]

8. Germany pubmed.ncbi.nlm.nih.gov

Patients' views about parathyroid transplantation for post-thyroidectomy hypoparathyroidism. [2023]

9. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Parathyroid transplantation in thyroid surgery. [2020]