Hypoparathyroidism PostproceduralNCT06499246
Parathyroid Allotransplant for Severe Refractory Hypoparathyroidism
A study testing Donor Parathyroid in people with Hypoparathyroidism Postprocedural, run by Karen Devon at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Hypoparathyroidism Postprocedural
- What is being tested?
- Donor Parathyroid
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2024to Jul 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- <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).
- Remote malignancies with successful treatment will not preclude patients from inclusion in the study. Dependent upon the malignancy risk level a minimal time from treatment will be required as established by the consensus recommendations outlined in Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement by Al-Adra et al.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
University Health Network
Toronto, Ontario, M5S1B2
Karen Devon, MD, MSc, FRCSC, FACS, 416236400 ext. 7352, karen.devon@wchospital.ca
About this study
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.
Read the detailed description
A protocol for deceased donor parathyroid transplantation was developed with the University Health Network Ajmera Transplant Centre in Toronto, relevant stakeholders, and presented to the innovation committee and REB for approval. Health Canada approval was obtained under the scope of existing cell tissue and organ regulations within the provincial organ procurement agency.
This is a pilot, prospective case-series. It includes a cohort of patients with hypoparathyroidism who will undergo parathyroid transplantation from a neurologically deceased donor. There is no control group in this study.
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.
All patients will have at least one pre-operative clinic visit with the endocrine surgery, endocrinology, and transplant team for comprehensive assessment. Baseline blood work will be conducted at this pre-operative visit, as outlined in the study protocol. The patient will also be evaluated by psychiatry and complete any necessary age appropriate comprehensive cancer screening as per standard transplantation protocol. Completeness of pre-transplant vaccinations (pneumococcus, HBV, influenza, Tdap, HAV) will be reviewed and arranged in co-ordination with patients' primary care provider as necessary. If based on pre-transplant work up a participant is deemed to meet exclusion criteria and not be suitable for transplant this will be discussed with the participant, and they will be withdrawn from the study. Participants will be informed of the need to fulfill the previously listed standard transplant criteria during the informed consent process.
Once a potential donor becomes available, the transplant team will decide whether the donor is a match for a study participant. A rigorous protocol for donor selection and transplantation was developed. Donor criteria aimed at minimizing infectious and immunological risks (HLA matching). A history of hyperparathyroidism (primary, secondary or tertiary) will also be screened for in the donor as the presence of hyperparathyroidism would be an exclusion criteria to procure their parathyroid glands for this study. If the donor is a match for a study participant, the participant will be contacted and timing of retrieval and patient arrival at TGH will be coordinated. The procurement team will then, with appropriate timing, procure all parathyroid tissue using standard surgical techniques and the tissue will be kept in organ preservation solution in a sterile specimen cup with a cold ischemic time of less than 2 hours.
The study participant will be admitted to the hospital under the Multi Organ Transplant team at TGH and will be taken to the operating room for the surgical procedure. The procedure will be performed under local anesthesia using a well-defined technique in the non-dominant brachioradialis muscle. The length of the surgery is estimated to be less than an hour. The patient will be recovering in PACU and then transferred back to the ward after the procedure is completed for continuation of the immunosuppressive therapy according to an established UHN Multiorgan Transplant protocol. After monitoring overnight, the patient will be discharged home the day following surgery.
The patient will be discharged home on day 1 post surgery and follow up will be arranged on day 3 and day 7 in for monitoring of calcium profile and response to treatment. Long-term follow-up for the patient will occur at 1, 3 and 12 months post-operatively with the endocrine surgery, endocrinology and transplant teams.
The primary outcomes of the study are to assess improvement in hypoparathyroidism as assessed by biochemistry and patient symptoms with secondary outcomes including risk of surgical complications.
- Conditions
- Hypoparathyroidism Postprocedural
- Being tested
- Donor Parathyroid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Donor ParathyroidProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Donor Parathyroid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Pre-operatively and then at 4 weeks, 3 months and 12 months post-operatively
Secondary outcomes (1)
Rate of surgical complications
Whether parathyroid allotransplant from neurologically deceased donors amongst patients with permanent refractory hypoparathyroidism has minimal surgical and medical complications and the need for medications.
Measured: 4 weeks, 3 months and 12 months post-operatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2024
- Study startJul 2024 (estimated)
- Primary completionJul 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hypoparathyroidism PostproceduralStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Parathyroid transplant from brain dead donors into patients with permanent hypoparathyroidism
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karen Devon
- Sponsor type
- University, hospital or other
- Collaborators
- University Health Network, Toronto, University of Toronto
- Responsible party
- Sponsor-investigator, Karen Devon, University Health Network, Toronto
- Investigators
- Karen Devon, MD, MSc, FRCSC, FACS, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06499246
- Sponsor's protocol ID
- 22-5129
- Status last verified
- Jul 2024
- First submitted
- 6 Jul 2024
- Last updated
- 12 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 34304848Devon 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.
PubMed 38919120
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Parathyroid Allotransplant for Severe Refractory Hypoparathyroidism
- ClinicalTrials.gov ID
- NCT06499246
- Acronym / sponsor ID
- 22-5129
- Conditions
- Hypoparathyroidism Postprocedural
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Karen DevonUniversity, hospital or other
- Collaborators
- University Health Network, Toronto, University of Toronto
- Study start
- Jul 2024 (estimated)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 12 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A protocol for deceased donor parathyroid transplantation was developed with the University Health Network Ajmera Transplant Centre in Toronto, relevant stakeholders, and presented to the innovation committee and REB for approval. Health Canada approval was obtained under the scope of existing cell tissue and organ regulations within the provincial organ procurement agency.
This is a pilot, prospective case-series. It includes a cohort of patients with hypoparathyroidism who will undergo parathyroid transplantation from a neurologically deceased donor. There is no control group in this study.
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.
All patients will have at least one pre-operative clinic visit with the endocrine surgery, endocrinology, and transplant team for comprehensive assessment. Baseline blood work will be conducted at this pre-operative visit, as outlined in the study protocol. The patient will also be evaluated by psychiatry and complete any necessary age appropriate comprehensive cancer screening as per standard transplantation protocol. Completeness of pre-transplant vaccinations (pneumococcus, HBV, influenza, Tdap, HAV) will be reviewed and arranged in co-ordination with patients' primary care provider as necessary. If based on pre-transplant work up a participant is deemed to meet exclusion criteria and not be suitable for transplant this will be discussed with the participant, and they will be withdrawn from the study. Participants will be informed of the need to fulfill the previously listed standard transplant criteria during the informed consent process.
Once a potential donor becomes available, the transplant team will decide whether the donor is a match for a study participant. A rigorous protocol for donor selection and transplantation was developed. Donor criteria aimed at minimizing infectious and immunological risks (HLA matching). A history of hyperparathyroidism (primary, secondary or tertiary) will also be screened for in the donor as the presence of hyperparathyroidism would be an exclusion criteria to procure their parathyroid glands for this study. If the donor is a match for a study participant, the participant will be contacted and timing of retrieval and patient arrival at TGH will be coordinated. The procurement team will then, with appropriate timing, procure all parathyroid tissue using standard surgical techniques and the tissue will be kept in organ preservation solution in a sterile specimen cup with a cold ischemic time of less than 2 hours.
The study participant will be admitted to the hospital under the Multi Organ Transplant team at TGH and will be taken to the operating room for the surgical procedure. The procedure will be performed under local anesthesia using a well-defined technique in the non-dominant brachioradialis muscle. The length of the surgery is estimated to be less than an hour. The patient will be recovering in PACU and then transferred back to the ward after the procedure is completed for continuation of the immunosuppressive therapy according to an established UHN Multiorgan Transplant protocol. After monitoring overnight, the patient will be discharged home the day following surgery.
The patient will be discharged home on day 1 post surgery and follow up will be arranged on day 3 and day 7 in for monitoring of calcium profile and response to treatment. Long-term follow-up for the patient will occur at 1, 3 and 12 months post-operatively with the endocrine surgery, endocrinology and transplant teams.
The primary outcomes of the study are to assess improvement in hypoparathyroidism as assessed by biochemistry and patient symptoms with secondary outcomes including risk of surgical complications.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Parathyroid transplant from brain dead donors into patients with permanent hypoparathyroidism
| Arm | Type | Receives |
|---|---|---|
| Parathyroid Transplant | Experimental | Procedure: Donor ParathyroidPatients 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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (7 listed)
- <18 years old male or female
- Current pregnancy
- Advanced stage 3-4 thyroid cancer
- Contraindication to surgery or immunosuppression
- Malignancy with contraindication to transplant:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Donor ParathyroidOnce 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. | Procedure or surgery | Parathyroid Transplant |
Primary outcome
Maintain calcium levels without standard calcium replacement treatment.
Time frame: Pre-operatively and then at 4 weeks, 3 months and 12 months post-operatively
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.
1 secondary outcome
Rate of surgical complications
Time frame: 4 weeks, 3 months and 12 months post-operatively
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2024.
- Background: PubMed 34304848Kim 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.
- Background: PubMed 38919120Devon 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Karen Devon, MD, MSc, FRCSC, FACS principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Donor Parathyroid in people with Hypoparathyroidism Postprocedural, run by Karen Devon at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Karen Devon, MD, MSc, FRCSC, FACS (416-323-6400 ext. 7352, karen.devon@wchospital.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maintain calcium levels without standard calcium replacement treatment. (time frame: Pre-operatively and then at 4 weeks, 3 months and 12 months post-operatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06499246, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2024.