A Registry for Participants With Chronic Hypoparathyroidism (PARADIGHM)

PARADIGHM (Physicians Advancing Disease Knowledge in Hypoparathyroidism): A Registry for Patients With Chronic Hypoparathyroidism

The main aim of this study is to find out the long-term safety and effectiveness profile of recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) treatment in participants with chronic hypoparathyroidism under conditions of routine clinical practice.

Participants will be treated according to their clinic's standard practice determined by the treating doctors. Each participant will fill out a study questionnaire during a routine doctor visit.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypoparathyroidism
• Intervention / Treatment: Other: No intervention

• Study Type: Observational
• Enrollment (Actual): 1339

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medizinische Universitaetsklinik Graz, Universitätsklinik Für Innere Medizin Graz
  • Vienna, Austria, 1090
    • AKH Wien, Universitaetsklinik fuer Innere Medizin III
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Nova Scotia Health Authority
  • Ontario
    • Oakville, Ontario, Canada, L6J IX8
      • McMaster University
• Denmark
  • Aalborg, Denmark, 9000
    • Aallborg University Hospital
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital
  • Hilleroed, Denmark, 3400
    • Nordsjaellands Hospital - Hillerod
  • Viborg, Denmark, 8800
    • Regions Hospitalet Viborg
• Germany
  • Aachen, Germany, 52074
    • Universitaetsklinik Aachen
  • Berlin, Germany, 10117
    • Charite-Universitiitsmedizin Berlin (CCM)
  • Berlin, Germany, 12159
    • Praxis an der Kaiserreiche
  • Dresden, Germany, 01307
    • Medizinische Fakultaet Carl Gustav Carus Technische Universitaet Dresden
  • Frankfurt, Germany, 60596
    • Endokrinologikum Frankfurt
  • Göttingen, Germany, 37075
    • MVZ endokrinologikum Göttingen
  • Lübeck, Germany, 23538
    • Universitaet Zur Luebeck
  • München, Germany, 81667
    • Medicover Neuroendokrinologie MVZ
  • Neu-Ulm, Germany, 89231
    • Medicover Neu-Ulm MVZ
  • Oldenburg, Germany, 26122
    • Medicover Oldenburg MVZ
  • Saarbrücken, Germany, 66111
    • Medicover Saarbuecken Mvz
  • Ulm, Germany, 89075
    • Endokrinologie Zentrum Ulm
  • Würzburg, Germany, 97080
    • Universitaetsklinikum Wuerzburg
  • Baden-Wurttemberg
    • Stuttgart, Baden-Wurttemberg, Germany, 70176
      • Diakonie-Klinikum Stuttgart
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Medizinische Hochschule Hannover
  • North Rhine-Westphalia
    • Düsseldorf, North Rhine-Westphalia, Germany, 40225
      • University Hospital Duesseldorf
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • University of Leipzig
• Greece
  • Athens, Greece, 11527
    • General Hospital of Athens Georgios Gennimatas
  • Athens, Greece, 11528
    • General Hospital of Athens Alexandra
  • Athens, Greece, 11526
    • General Hospital Of Athens - Korgialenio-Benakio E.E.S.
  • Thessaloniki, Greece, 54636
    • Ahepa University General Hospital of Thessaloniki
  • Thessaloniki, Greece, 54642
    • Hippokrateion General Hospital of Thessaloniki
• Italy
  • Florence, Italy, FI 50139
    • Azienda Ospedaliero-Universitaria Careggi
  • Milan, Italy, MI 20122
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
  • Roma, Italy, RM 00184
    • Azienda Ospedaliera San Giovanni Addolorata
  • Torino, Italy, TO 10126
    • Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza - Ospedale Molinette
• Norway
  • Bergen, Norway, 5012
    • Haukeland University Hospital
  • Oslo, Norway, 0176
    • Spesialistsentret Pilestredet Park
• Spain
  • Barcelona, Spain, 08003
    • Hospital Del Mar
  • Granada, Spain, 18016
    • Hospital Universitario San Cecilio
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
• Sweden
  • Linköping, Sweden, 58185
    • Universitetssjukhuset i Linköping
  • Stockholm, Sweden, 17176
    • Karolinska Universitetssjukhuset Solna
  • Uppsala, Sweden, 75185
    • Akademiska Sjukhuset - Uppsala University Hospital
  • Örebro, Sweden, 70185
    • Universitetssjukhuset I Orebro
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • University of Hospitals of Leicester
  • Norwich, United Kingdom, NR4 7UQ
    • Norfolk And Norwich University Hospital - Norwich Medical School
  • England
    • Birmingham, England, United Kingdom, B15
      • Queen Elizabeth Hospital-Mindelsohn Way
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85714
      • University of Arizona Medical Center
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • San Jose, California, United States, 95148
      • Dr. Joselito Cabaccan
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • Florida
    • Port Charlotte, Florida, United States, 33952
      • Hanson Clinical Research Center
    • Sarasota, Florida, United States, 34239
      • Thyroid & Endocrine Center of Florida
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Suburban Endocrinology & Diabetes
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Evanston, Illinois, United States, 60201
      • Northshore University Health System
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Hospital
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tilak Mallik, MD F.A.C.E., LCC
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • MedStar Union Memorial Hospital
    • Baltimore, Maryland, United States, 21204
      • Model Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02115
      • Harvard Medical School
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Diabetes & Endocrine Associates, Methodist Physicians Clinic Diabetes and Endocrine Specialists
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Palm Research Center, Inc.
    • Reno, Nevada, United States, 89511
      • Northern Nevada Endocrinology
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Robert Wood Johnson Medical School
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers-Robert Wood Johnson Medical School
  • New York
    • Albany, New York, United States, 12206
      • Albany Med Endocrine Specialists
    • Brooklyn, New York, United States, 11223
      • Brokhin Medical PC
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10022
      • Gerald Friedman Diabetes Institute
    • Smithtown, New York, United States, 11787
      • Endocrine Associates of Long Island, P.C.
    • Staten Island, New York, United States, 10301
      • University Physicians Group Research Division
    • Syracuse, New York, United States, 13214
      • State University of New York Upstate Medical University
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Mecklenburg Medical Group
    • Greenville, North Carolina, United States, 27834
      • Physicians East, PA
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • Ohio State University Wexner Medical Center
    • Columbus, Ohio, United States, 43214
      • Ohio Health Research Institute
  • Pennsylvania
    • Indiana, Pennsylvania, United States, 15701
      • Endocrinology Associates of Armstrong
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 76307
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15212
      • Alleghany General Hospital
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Hallett Center for Diabetes and Endocrinology
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • University of South Carolina
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Diabetes and Endocrinology, P.A.
    • Dallas, Texas, United States, 75208
      • Thyroid Endocrinology and Diabetes
    • El Paso, Texas, United States, 79935
      • Academy of Diabetes Thyroid and Endocrine
    • Fort Worth, Texas, United States, 76132
      • Diabetes and Thyroid Center of Fort Worth, PLLC
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • University of Vermont
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This global registry is expected to enroll a minimum of 900 participants, of whom at least 300 will be participants treated with rhPTH(1-84) and at least 600 will be participants receiving standard of care. Protocol amendment 9 revised the sample size: up to 164 additional participants treated with rhPTH(1-84) (ie, up to a total of 464 participants in that cohort) will be enrolled as needed to ensure the availability of 104 rhPTH(1-84)-treated participants with a full 10 years of follow-up.

Description

Inclusion Criteria:

• Participants diagnosed with chronic hypoparathyroidism, that is, hypoparathyroidism with a duration of longer than 6 months, including:

  1. Adult participants (greater than or equal to [>=] 18 years of age) who are receiving for chronic hypoparathyroidism any of the following options: standard therapy, standard therapy plus rhPTH(1-84), or rhPTH(1-84) therapy alone.
  2. Pediatric participants (less than [<] 18 years of age) who are receiving for chronic hypoparathyroidism any of the following options: standard therapy, standard therapy plus rhPTH(1-84), or rhPTH(1-84) therapy alone.

Exclusion Criteria:

• Participants or legally acceptable representatives unable to provide informed consent.
• Participants using rhPTH(1-34) or who used rhPTH(1-34) for more than 2 years are excluded. Participants who had been treated with rhPTH(1-34) within 3 months of enrollment are also excluded as are participants currently using rhPTH(1-34).

FOR US SITES ONLY: Participants treated with rhPTH(1-84) prior to the US recall may use rhPTH(1-34) only while rhPTH(1-84) is unavailable due to the recall.

• Participants currently enrolled in an interventional clinical study (whether or not the study is related to hypoparathyroidism); note that this does not include participants enrolled in other observational registries.
• History of hypoparathyroidism resulting from impaired responsiveness to PTH (pseudohypoparathyroidism).

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Natpar(a); Participants receiving parathyroid hormone (rhPTH(1-84) (Natpar[a]) for treatment of chronic hypoparathyroidism as per standard clinical practice will be enrolled and evaluated during the study period.	Other: No intervention; This is a non-interventional study.
Conventional Therapy; Participants receiving conventional therapy/standard of care (including calcium supplements, active vitamin D, vitamin D) for treatment of chronic hypoparathyroidism as per standard clinical practice will be enrolled and evaluated during the study period.	Other: No intervention; This is a non-interventional study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in 24-Hour Urine Calcium	Change from baseline in 24-hour urine calcium will be evaluated.	Baseline up to 10 years (follow-up)
Change from Baseline in Serum Calcium	Change from baseline in serum calcium will be evaluated.	Baseline up to 10 years (follow-up)
Change from Baseline in Serum Albumin	Change from baseline in serum albumin will be evaluated.	Baseline up to 10 years (follow-up)
Change from Baseline in Albumin-Corrected Total Calcium	Change from baseline in albumin-corrected total calcium will be evaluated.	Baseline up to 10 years (follow-up)
Change from Baseline in Serum Ionized Calcium	Change from baseline in serum ionized calcium will be evaluated.	Baseline up to 10 years (follow-up)
Change from Baseline in Serum Magnesium	Change from baseline in serum magnesium will be evaluated.	Baseline up to 10 years (follow-up)
Change from Baseline in Serum Phosphate	Change from baseline in serum phosphate will be evaluated	Baseline up to 10 years (follow-up)
Change from Baseline in 25-Hydroxy (25-OH) Vitamin D results	Change from baseline in 25-OH vitamin D will be evaluated.	Baseline up to 10 years (follow-up)
Change from Baseline in Serum Creatinine	Change from baseline in serum creatinine will be evaluated.	Baseline up to 10 years (follow-up)
Change from Baseline in Estimated Glomerular Filtration Rate (eGFR; calculated)	Change from baseline in eGFR; calculated will be evaluated.	Baseline up to 10 years (follow-up)
Change from Baseline in 24-Hour Urine Protein	Change from Baseline in 24-hour urine protein will be evaluated.	Baseline up to 10 years (follow-up)
Incidence Rate of the Renal Events	Incidence rate of the renal events will be recorded for nephrolithiasis, nephrocalcinosis, hospitalization/emergency room visits for renal events.	Baseline up to 10 years (follow-up)
Incidence Rate of the Soft Tissue Calcifications (site)	Incidence rate of the soft tissue calcifications (site) will be recorded.	Baseline up to 10 years (follow-up)
Incidence Rate of the Cataract	Incidence rate of the cataract will be recorded by questionnaire (present/not present).	Baseline up to 10 years (follow-up)
Incidence Rate of the Bone Fractures (site)	Incidence rate of the bone fractures (site) will be recorded.	Baseline up to 10 years (follow-up)
Incidence Rate of the Cardiovascular Events	Incidence rate of the cardiovascular events will be calculated for this clinical outcome. Cardiovascular events include myocardial infarction, stroke, arrhythmia.	Baseline up to 10 years (follow-up)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, a new disease or worsening in severity or frequency of a concomitant disease, temporally associated with the use of a medicinal product, whether or not the event is considered causally related to the use of the product. An SAE is any untoward medical occurrence (whether considered to be related to study product or not) that at any dose results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality or birth defect, an important medical event.	Baseline up to 10 years (follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related Quality of Life (HRQoL)	Health-Related Quality of Life (HRQoL), as measured by the short-form-10 (SF-10) for pediatrics, short-form-36 (SF-36) for adults will be examined longitudinally using methods for continuous data.	Baseline up to 10 years (follow-up)
Disease-specific Patient-reported Outcome Measures	Chronic hypoparathyroidism patient-reported outcome will be recorded as measured by the hypoparathyroidism multi-symptom diary (HPT-SD).	Baseline up to 10 years (follow-up)
Rate of Hospitalization/Emergency Room (ER) Visits	The rate of hospitalizations and ER visits during follow-up will be summarized.	Baseline up to 10 years (follow-up)

Collaborators and Investigators

• Sponsor: Takeda
• Collaborators: Takeda Development Center Americas, Inc.
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

General Publications

• Gittoes N, Rejnmark L, Ing SW, Brandi ML, Bjornsdottir S, Hahner S, Hofbauer LC, Houillier P, Khan AA, Levine MA, Mannstadt M, Shoback DM, Vokes TJ, Zhang P, Marelli C, Germak J, Clarke BL. The PARADIGHM (physicians advancing disease knowledge in hypoparathyroidism) registry for patients with chronic hypoparathyroidism: study protocol and interim baseline patient characteristics. BMC Endocr Disord. 2021 Nov 20;21(1):232. doi: 10.1186/s12902-021-00888-2.

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2013
• Primary Completion (Estimated): November 30, 2034
• Study Completion (Estimated): November 30, 2034

Study Registration Dates

• First Submitted: August 1, 2013
• First Submitted That Met QC Criteria: August 13, 2013
• First Posted (Estimated): August 14, 2013

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Observational study; rhPTH(1-34); parathyroid hormone (PTH); Chronic Hypoparathyroidism; rhPTH(1-84); Drug registry
• Additional Relevant MeSH Terms: Endocrine System Diseases; Parathyroid Diseases; Hypoparathyroidism
• Other Study ID Numbers: PAR-R13-001; EUPAS16927 (Other Identifier: ENCePP EU PAS)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes