Parathyroid tissue transplant into the forearm for chronic hypoparathyroidism

Parathyroid Allotransplant for Treatment of Hypoparathyroidism: PATTH

This project will try transplanting donated parathyroid tissue into the forearm of adults with chronic hypoparathyroidism to raise PTH and help normalize their calcium and phosphorus levels.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 3 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Francisco (Academic / other)
• Locations: 1 site (San Francisco, California)
• Trial ID: NCT06961071 on ClinicalTrials.gov

What this trial studies

This Phase 1/2, first-in-human protocol uses cadaveric donor parathyroid tissue implanted into the forearm with the goal of restoring parathyroid hormone (PTH) production. Participants are adults with chronic post-surgical or postprocedural hypoparathyroidism who meet specific biochemical and treatment criteria. The study will monitor PTH, serum calcium and phosphorus, and clinical symptoms while managing immunosuppression and safety outcomes. The procedure is investigational, conducted at UCSF with NIH collaboration, and intended as an alternative given anticipated discontinuation of a commercial PTH product.

Who should consider this trial

Good fit: Adults (≥18) with chronic hypoparathyroidism (≥12 months post-surgery or postprocedural), documented low or inappropriately normal PTH on repeat testing, requiring activated vitamin D and oral calcium or with ongoing symptoms on PTH replacement, who can consent and are eligible for immunosuppression and follow-up are the intended candidates.

Not a fit: Patients who cannot tolerate or are ineligible for immunosuppression, have immunodeficiency or active infections, or who do not meet the biochemical and treatment-duration criteria are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, the transplant could restore steady PTH production and reduce or eliminate the need for high-dose oral calcium, activated vitamin D, or injectable PTH therapies.

How similar studies have performed: This approach is largely novel in humans with only limited case reports and experience from autotransplantation; there are no large, established clinical trials showing consistent success with cadaveric parathyroid allotransplantation.

Eligibility criteria

Inclusion Criteria Only subjects who meet all of the following criteria are eligible for enrollment.

1. Subjects age 18 or older.
2. Subjects who are able to provide written informed consent and to comply with study procedures.
3. Clinical history and laboratory data compatible with HypoPT as defined by hypocalcemia and documented PTH levels either inappropriately normal or below the normal range on two occasions greater than 2 weeks apart and 12 months after surgery, requiring treatment with activated vitamin D (≥0.5 mcg calcitrol) and oral calcium (≥800mg) daily, or currently on PTH (1-84), PTH (1-34), palopegteriparatide or other recombinant parathyroid hormone replacement injections with ongoing symptomatology due to hypocalcemia and variable degree of biochemical control.
4. No history of immunodeficiency (e.g., opportunistic infections) that could be exacerbated by immunosuppression.
5. Up to date immunizations per the University of California, San Francisco (UCSF) standard of care for organ transplantation, including influenza, pneumococcal, hepatitis B, and tetanus-diptheria

Exclusion Criteria Subjects who meet any of the following criteria are not eligible for enrollment

1. Presence of donor specific anti-HLA antibodies detected by Luminex Single Antigen/specificity bead assay including weakly reactive antibodies that would not be detected by a flow cross match
2. Intolerance to any drug that will be used as part of the IS regimen.
3. Poorly controlled diabetes with an A1C of \>8%.
4. Blood Pressure (BP): systolic blood pressure (SBP) \> 140mmHg or DBP \>90 mmHg despite treatment with antihypertensive agents. If the BP is greater than 140/90 chart review and discussion with the patient will be done to establish that BP is in good control.
5. Other exclusion criteria including significant renal or hepatic dysfunction
6. For female subjects: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception. Oral contraceptives, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
7. Active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB). Quantiferon gold assay will be used to determine TB infection.
8. Invasive aspergillus, histoplasmosis, and coccidioidomycosis infection or other opportunistic infection within 1 year prior to study entry.
9. Current malignancy or treated malignancy with estimated recurrence rate \>50% at 5 years, except for completely resected squamous or basal cell carcinoma of the skin
10. Known active alcohol or substance abuse.
11. Active infections (except mild skin and nail fungal infections).
12. Active peptic ulcer disease or gastritis, symptomatic gallstones, or portal hypertension.
13. Use of any investigational agents within 4 weeks of screening or 5 half-lives of the investigational product/ medication, whichever is longer. Investigational products with prolonged invivo effects will require a wash-out period that aligns with the biochemical and physiologic effects of the agent prior to the initiation of this protocol. If the half life of the experimental agent is not known, participation in the study will be addressed with the study team and documented in the study record.
14. Any investigational agents/products that could potentially interfere with the safety and/or efficacy of the procedure being studied will be addressed with the study team and documented in the study record.
15. Administration of live attenuated vaccine(s) within 2 months of enrollment.
16. Any medical condition that, in the opinion of the investigator, will interfere with safe study completion.
17. Positive screen for polyoma (BK) viremia at time of screening.
18. CKD stage 4 or 5
19. Severe co-existing cardiac disease, characterized by any one of these conditions:

    1. Recent myocardiol infarction (MI) (within 1 year)
    2. Evidence of ischemia on functional cardiac exam within the last year. These include persantine thallium stress test and/or coronary angiogram which will be performed in any patient with a history of an MI
    3. Left ventricular ejection fraction \< 45%
    4. Valvular disease requiring replacement with prosthetic valve
20. Substance use that in the opinion of the investigator would interfere with compliance with the study requirements.
21. Past or current medical problems or findings from medical history, physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Where this trial is running

San Francisco, California

• University of California, San Francisco — San Francisco, California, United States (Recruiting)

Study contacts

• Principal investigator: Peter Stock, MD, PhD — University of California, San Francisco
• Study coordinator: Crystal Loucel, MPH, MS, RN

Conditions Hypoparathyroidism; Hypoparathyroidism Postprocedural; Hypoparathyroidism Post-surgical; hypoparathyroidism; parathyroid hormone; PTH; serum calcium; phosphorus