Parathyroid Transplant for Hypoparathyroidism

(PATH Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Brenessa Lindeman, MD, MEHP

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Alabama at Birmingham

Must not be taking: Immunosuppressants

Disqualifiers: Active malignancy, Uncontrolled diabetes, Severe osteoporosis, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Options for treatment of severe, refractory hypocalcemia are limited for the thousands of patients in the United States who suffer from hypoparathyroidism. Parathyroid allotransplantation is an emerging treatment that provides hope for these individuals. Currently, this therapy has only been successfully provided by a few centers in the world. In the UAB PATH trial, we propose to become one of the few centers worldwide to successfully achieve parathyroid allotransplantation in transplant-naïve patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves a transplant, you may need to take immunosuppressive drugs, which could affect your current medication regimen.

What data supports the effectiveness of the treatment Parathyroid Allotransplantation for Hypoparathyroidism?

Research shows that parathyroid allotransplantation can be an effective alternative to traditional treatments like vitamin D3 and calcium supplements for managing hypoparathyroidism. In a study involving 85 patients, long-term activity of transplanted parathyroid cells was observed, suggesting its potential effectiveness. ^{1 2 3 4 5}

Is parathyroid transplantation safe for humans?

Parathyroid allotransplantation has been studied as a treatment for hypoparathyroidism, and reviews of case studies suggest it is generally safe, although it requires specialized staff and equipment. ^{1 3 4 6 7}

How is parathyroid allotransplantation different from other treatments for hypoparathyroidism?

Parathyroid allotransplantation is unique because it involves transplanting healthy parathyroid tissue from a donor to a patient, which can restore natural hormone production, unlike standard treatments that rely on supplements like vitamin D and calcium. This method can potentially eliminate the need for lifelong medication, but it requires specialized equipment and expertise, making it a complex and costly procedure. ^{1 2 3 4 5}

Research Team

Brenessa Lindeman, MD, MEHP

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for adults aged 18-80 with hypoparathyroidism caused by neck surgery, congenital issues, or treatment failure. They must have had the condition for at least a year and live near Birmingham. Participants need to speak English and commit to the trial's process. Exclusions include active cancer (except skin), severe heart/liver/kidney/brain diseases, uncontrolled diabetes, clotting disorders, psychiatric illness, osteoporosis, allergies to immunosuppressants, non-adherence to medical therapies.

Inclusion Criteria

I have low calcium due to a neck surgery that affected my parathyroid glands.

I have low calcium due to underdeveloped parathyroid glands.

I have low calcium due to hypoparathyroidism for over a year.

Exclusion Criteria

You are allergic or highly sensitive to certain medications that can weaken the immune system.

I rely on a nursing home or long-term care for my daily needs.

I quit smoking more than 3 months ago.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Virtual consults and in-person visits at MD discretion

Pre-graft function

Daily phone check-ins with labs every other day and clinic visits twice weekly with ultrasound of graft

2 weeks

Post-graft function

Weekly labs and clinic visits for 3 months, followed by monthly visits for 1 year

15 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Parathyroid Allotransplantation (Procedure)

Trial Overview The UAB PATH trial is testing parathyroid allotransplantation as a new treatment option for patients with medically refractory hypocalcemia due to hypoparathyroidism. This innovative procedure aims to provide relief where other treatments have failed.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Kierstin Kennedy

University of Alabama at Birmingham

Chief Medical Officer since 2022

MD

S. Dawn Bulgarella

University of Alabama at Birmingham

Chief Executive Officer since 2023

BSc in Commerce and Business Administration from the University of Alabama, MS in Health Administration from the University of Alabama at Birmingham

Findings from Research

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]

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 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 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]

Parathyroid allotransplantation shows a mean graft survival rate of 47% at 6 months and 41% at 12 months in patients with post-thyroidectomy hypoparathyroidism, based on a review of 9 studies involving 146 patients.

While some evidence suggests that parathyroid hormone (PTH) and serum calcium levels remain elevated post-transplantation, the long-term benefits and risks of this treatment remain unclear due to significant variability among the studies, highlighting the need for further controlled clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parathyroid allotransplantation to treat post-thyroidectomy hypoparathyroidism: A review of case studies. Parameswaran, R., Samuel, M., Satish, RL., et al.[2021]

References

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

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

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

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

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

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

4. Turkey pubmed.ncbi.nlm.nih.gov

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

5. 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]

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

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

7. Scotland pubmed.ncbi.nlm.nih.gov

Parathyroid allotransplantation to treat post-thyroidectomy hypoparathyroidism: A review of case studies. [2021]