Parathyroid Allotransplant for Severe Refractory Hypoparathyroidism

NCT06499246 | Recruiting

• 1 other identifier: 22-5129
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypoparathyroidism Postprocedural

Outcome Measures

Primary Outcomes (1)

• Maintain calcium levels without standard calcium replacement treatment.

  Patients will demonstrate improvement in hypocalcemia symptoms, biochemical calcium profile, and parathyroid hormone levels as well as decrease frequency of emergency visits for intravenous calcium. Specifically at each assessment patients will be questioned regarding numbness and tingling and will be examined for presence of Chvostek's and Trousseau's sign. Additionally, to assess overall impact of symptoms in relation to quality of life. A hypoparathyroidism quality-of-life questionnaire will be filled out by the patient pre-operatively and at 12 months post-operatively. This questionnaire was formulated and has been used for research purposes by the HypoParaUK group. Biochemical calcium profile (serum total calcium, albumin, ionized calcium, parathyroid hormone level, vitamin D level, phosphate) using blood tests done on post-operative day 1, 3, 5, 7, and subsequently 2 weeks, 3 weeks, 4 weeks post-operatively, and afterwards monthly for a total of 12 months post-operatively.

  Pre-operatively and then at 4 weeks, 3 months and 12 months post-operatively

Secondary Outcomes (1)

• Rate of surgical complications

  4 weeks, 3 months and 12 months post-operatively

Study Arms (1)

Parathyroid Transplant

EXPERIMENTAL

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.

Procedure: Donor Parathyroid

Interventions

Donor Parathyroid PROCEDURE

Once a potential donor becomes available, the transplant team will assess if the donor is a match for our study participant using standardized transplantation protocols that include serology blood tests completed in the pre-operative setting. If the donor is a match, the procurement team will procure all parathyroid tissue using standard surgical techniques. The specimen will be kept in organ preservation solution for transport and transported to the operating room. The recipient (study participant) will be admitted to the hospital under and taken to the operating room for the surgical procedure. Once the procurement team arrives with the parathyroid tissue the procedure will be performed under local anesthesia using a well-established technique, for parathyroid auto transplant, of implanting parathyroid tissue in the non-dominant brachioradialis muscle. Immunosuppression medication protocols will be initiated.

Parathyroid Transplant

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior total thyroidectomy
• Symptomatic hypocalcemia (numbness, tingling, or other neurologic symptoms) requiring daily high dose calcium (greater than 2000 mg per day) and vitamin D (greater than 2 mcg of calcitriol per day) supplementation and/or intermittent IV calcium infusion.
• Biochemical blood test consistent with hypoparathyroidism
• Failed medical management (\>1 year of post-thyroidectomy hypoparathyroidism treated medically with persistent biochemical disease and symptoms)
• Patient meets current standards for receiving an organ transplant (e.g. no active infection, no malignancy, no contraindications to immunosuppression or surgery)

You may not qualify if:

• \<18 years old male or female
• Current pregnancy
• Advanced stage 3-4 thyroid cancer
• Contraindication to surgery or immunosuppression
• Malignancy with contraindication to transplant:
• Certain active malignancies are not a contraindication to transplant such as prostate cancer or lymphoproliferative disease in remission, and locoregional skin malignancies such as melanoma will be transplant candidates (outlined in Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement by Al-Adra et al respectively).

Sponsors & Collaborators

• Karen Devon: lead
• University Health Network, Toronto: collaborator
• University of Toronto: collaborator

Study Sites (1)

University Health Network

Toronto, Ontario, M5S1B2, Canada

RECRUITING

Related Publications (2)

• Kim E, Ramonell KM, Mayfield N, Lindeman B. Parathyroid allotransplantation for the treatment of permanent hypoparathyroidism: A systematic review. Am J Surg. 2022 Apr;223(4):652-661. doi: 10.1016/j.amjsurg.2021.07.025. Epub 2021 Jul 20.

  PMID: 34304848 BACKGROUND

• Devon K, Tinckam K, Humar A, Madani A, Pasternak JD, Saravana-Bawan B, Zahedi A. Successful Deceased Donor Parathyroid Allotransplantation: A Novel Approach in a Patient with Severe Refractory Hypoparathyroidism After Thyroidectomy for Thyroid Cancer. Thyroid. 2024 Aug;34(8):1058-1061. doi: 10.1089/thy.2024.0115. Epub 2024 Jul 18. No abstract available.

  PMID: 38919120 BACKGROUND

Study Officials

• Karen Devon, MD, MSc, FRCSC, FACS

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karen Devon, MD, MSc, FRCSC, FACS

CONTACT

416-323-6400; karen.devon@wchospital.ca

Esther Lee, BScN

CONTACT

416-340-4800; esther.lee@uhn.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: It is open label. No masking involved.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Surgery

Model Details: Parathyroid transplant from brain dead donors into patients with permanent hypoparathyroidism

Study Record Dates

• First Submitted: July 6, 2024
• First Posted: July 12, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: July 12, 2024

Record last verified: 2024-07

Locations

CA (1)