Clinical Trial: ADD-ON Study to Existing Hypoparathyroidism Studies

Study Status: Active, not recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Phase II Trial of Parathyroid Hormone for the Treatment of Hypoparathyroidism

Brief Summary:

The purpose of this protocol is to add on additional exploratory studies to investigate changes in bone quality parameters with PTH(1-84) treatment of hypoparathyroidism. In addition to the biochemical hallmarks of hypoPT, it has been found that the microscopic structure of the bone, as well as the bone remodeling system, are markedly abnormal in this disease. How these abnormalities may be corrected with PTH(1-84) administration are not fully understood. The studies outlined in this add-on protocol are designed to shed light on the mechanistic ways that PTH(1-84) replacement may restore normal bone metabolism. These mechanistic studies are beyond the scope of the parent NPS study, which was designed to assess the safety and efficacy of PTH(1-84) in hypoPT treatment. Subjects who are participating in the NPS' REPLACE, RELAY, and RACE Studies and the HEXT Study at Columbia University will be invited to participate in this add-on protocol, which will involve a separate IRB-approved informed consent.

Study procedures:

  1. High Resolution Peripheral Quantitative Computed Tomography (HRpQCT; XtremeCT, Scanco): Done at the same visit as DXA. In the REPLACE study twice, in RELAY once (or not at all if done within the last 6 months), in RACE twice, and in HEXT three times.
  2. Osteolineage: At Baseline/Randomization/Visit One and at 4, 8, 12, 24, and 52 weeks of treatment in the REPLACE, RELAY, or RACE Study, if applicable, or at baseline and each 6-months visit in the HEXT Study, blood test for circulating osteogenic cells (10 cc) will be performed
  3. Sclerostin: At Baseline/Randomization/Visit One and at 4, 8, 12, 24, and 52 weeks of treatment in the REPLACE, RELAY, or RACE Study, if applicable, or at baseline and each 6-months visit in th

    Detailed Summary:

    In this protocol, we will investigate the mechanisms by which PTH(1-84) treatment improves bone quality in patients with hypoparathyroidism. Detailed imaging, cellular and biochemical studies will be performed on subjects with hypoparathyroidism who are also participating in the NPS Pharmaceutical Company's studies known as REPLACE, RELAY, RACE studies, and IND70449's HEXT Study. The parent NPS trial, being conducted under NPS's IND #76,514, is a multi-site, randomized, double-blind, placebo-controlled trial of PTH(1-84) in hypoparathyroidism. In the REPLACE Study, hypoparathyroid subjects are assigned to either placebo, 50, 75 or 100 mcg of PTH(1-84) a day, in a dose-titration design, for a 26 week period. In RELAY Study hypoparathyroid patients are randomized to 25mcg or 50mcg PTH1-84 for 8 weeks. In the RACE Study hypoparathyroid patients utilize 25, 50, 75, or 100mcg PTH1-84 for 52 weeks. The primary efficacy endpoint is a 50% reduction in calcium and calcitriol supplementation. The Columbia site is one of the investigative sites for the NPS protocol. A letter from NPS accompanying this document certifies that Dr. Bilezikian is a subinvestigator in the NPS project.

    The protocol described in this proposal is different from the NPS study. It is being conducted under IND #70,449 to Dr. Bilezikian. It will pursue a number of additional studies that are not being sponsored by NPS or covered by their IND. Under IND #70,449 assigned to Dr. Bilezikian, we will investigate the effects of PTH(1-84) administration in hypoparathyroidism on bone quality in hypoparathyroidism. In addition to the biochemical hallmarks of hypoparathyroidism, it has been found that the microarchitectural structure of the bone and the entire bone remodeling system are markedly abnormal in this disease. The studies outlined in this add-on protocol are designed to elucidate the specific ways in which PTH
    Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    Current Primary Outcome:

    • HRpQCT [ Time Frame: before and after treatment ]
      HPpQCT is performed twice in the REPLACE Study, one at Baseline, and again at 6 months. In the RELAY Study it is performed once at baseline, and only if it has not be done within the last 6 months. In the RACE study it is performed twice, once at baseline, then again at 52 weeks. In the HEXT study it is performed three times, once at baseline, then at 12 and 24 months.
    • sclerostin [ Time Frame: variable depending on parent study ]
      At Baseline/Randomization/Visit One and at 4, 8, 12, 24, and 52 weeks of treatment in the REPLACE, RELAY, or RACE Study, if applicable, or at baseline and each 6-months visit in the HEXT Study. 5cc per draw.
    • circulating osteogenic precursors [ Time Frame: variable depending on parent study ]
      At Baseline/Randomization/Visit One and at 4, 8, 12, 24, and 52 weeks of treatment in the REPLACE, RELAY, or RACE Study, if applicable, or at baseline and each 6-months visit in the HEXT Study. 10cc per draw.


    Original Primary Outcome: serum calcium [ Time Frame: every 3 months ]

    Current Secondary Outcome:

    Original Secondary Outcome: dual x-ray absorptometry (DXA) [ Time Frame: every 6 months ]

    Information By: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    Dates:
    Date Received: March 4, 2009
    Date Started: September 2010
    Date Completion: September 2014
    Last Updated: June 12, 2014
    Last Verified: June 2014