Recombinant Human rhPTH(1-34) VS Association Alfacalcidol/Hydrochlorothiazide in Severe Primary Hypoparathyroidism

• Status: Completed
• Trial end date: 2020-05-28
• Target enrollment: 0
• Participant gender: All

Summary

Hypoparathyroidism is a rare condition in which the parathyroid glands fail to produce sufficient amount of parathyroid hormone or the parathyroid hormone produced lacks biologic activity. The most common cause of hypoparathyroidism is damage to or removal of the parathyroid glands due to neck surgery for another condition. Occurrence of hypercalciuria under treatment is a frequent concern in primary hypoparathyroidism, limiting correction of hypocalcemia.

Hypoparathyroidism can also be caused by an autoimmune process. In rare cases, hypoparathyroidism may occur as a genetic disorder inherited as an autosomal recessive, autosomal dominant or X-linked recessive trait. The autosomal dominant hypocalcemia (ADH) is mainly caused by heterozygous activating mutations in the CASR gene encoding CaSR). As other severe presentation of primary hypothyroidism, ADH is characterized by the increased risk to develop hypercalciuria and nephrolithiasis. The purpose of the study is to compare two therapeutic approaches in severe hypoparathyroidism in order to limit the risk of nephrocalcinosis and renal failure when attempting to correct hypocalcemia: rhPTH(1-34) vs association of active vitamin D and hydrochlorothiazide. The European Society of Endocrinology Clinical has indeed recently published guidelines for the treatment of chronic hypoparathyroidism in adults. These guidelines suggest considering treatment with a thiazide diuretic In a patient with hypercalciuria and replacement therapy with PTH in patients who do not stably and safely maintain their serum and urinary calcium in the target range.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Ministry of Health, France
• Treatments: Alfacalcidol; Diuretics; Diuretics, Potassium Sparing; Hydrochlorothiazide; Hydroxycholecalciferols; Sodium Channel Blockers; Teriparatide

Criteria

Inclusion criteria :

• Patients aged from 18 to 80 years, of both sexes

• Patient with primary hypoparathyroidism related to a genetically proven ADH OR primary hypoparathyroidism related to other cause but complicated by hypercalciuria under treatment

• Affiliated to a French health insurance system, and who have consented to the study.

Exclusion criteria :

• Pregnant and breastfeeding women;

• Women of childbearing age without contraception;

• For men aged from 18 to 20 years, presence of cartilage of growth on X-ray of left knee;

• Anuria;

• Kidney failure with plasmatic creatinine >125 mmol/l and urea >10 mmol/l;

• Long QT interval : QTc > 450 ms (men) or 470 ms (women);

• Hepatic failure;

• Metabolic bone diseases (Paget's disease of bone) other than primary osteoporosis or glucocorticoid-induced osteoporosis;

• Association to other potassium sparing diuretics;

• Hypokalemia (<3.5 mmol/l) without diuretic therapy;

• Hyperkalemia (>5.5 mmol/l);

• Hyponatremia (<135 mmol/l) without diuretic therapy;

• Hypercalcemia (>2.6 mmol/l);

• Severe hypomagnesemia (≤ 0.5 mmol/l);

• Vitamin D deficiency (25OH vit D < 20 ng/mL);

• Unexplained increase in alkaline phosphatase (>2N);

• Intolerance to sulfamide;

• Intolerance to amiloride or other component of the drug;

• Hypersensitivity to any active substance or excipient of one of the experimental drugs;

• Gluten intolerance;

• Bone break history within the three previous months;

• History of radiotherapy of the skeleton;

• History of bone cancer or metastasis.

• Personnal or familial (first degree relatives) of skin cancer