Treatment of Hypoparathyroidism With Subcutaneous PTH (1-84) Injections: Effects on Muscle Function and Quality of Life (HypoPTH)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Aarhus
ClinicalTrials.gov Identifier:
NCT00730210
First received: August 4, 2008
Last updated: October 23, 2012
Last verified: October 2012
  Purpose

The aim of the study is to assess whether PTH (1-84) therapy posses advantages compared to conventional treatment in patients with hypoparathyroidism on muscle function, quality of life, calcium homeostasis, bone metabolism, and body composition.


Condition Intervention Phase
Hypoparathyroidism
Drug: a: PTH (1-84)
Drug: b:placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Hypoparathyroidism With Subcutaneous PTH (1-84) Injections: Effects on Muscle Function and Quality of Life

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • Increase in maximal voluntary knee extension [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Balance function: Is assessed using a stadiometer (Meititur Ltd, Finland) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Effect of treatment on indices of quality of life is assessed using the SF-36v2- and WHO-Five Well-Being Index (WHO-5)-survey. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Effects of treatment on muscle function are assessed through muscle biopsies, electromyographic, and by biochemical measures (muscle enzymes). [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Bone mineral density and body composition is measured [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Calcium homeostasis and bone metabolism. Effects of treatment are assessed by measurements of calcitropic hormones, biochemical markers of bone turnover, and bone biopsies [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Q CT scan of hip and spine [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Effects of treatment on diurnal variations of measured biochemical indices, as assessed at the end of the treatment period [ Time Frame: 24 hours at the end of the 6 month treatment period ] [ Designated as safety issue: No ]
  • Effects of treatment on indices of cardiovascular health (ECG and blood pressure), as measured at the end of the treatment period just prior to and 1 hour after injection of study medication. [ Time Frame: at the end of the 6 months treatment period ] [ Designated as safety issue: Yes ]

Enrollment: 62
Study Start Date: June 2008
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: a: PTH (1-84) 100 ug s.c.inj. once a day
PTH (1-84) 100 ug subcutaneous injections once a day
Drug: a: PTH (1-84)
preotact 100 microgram subcutaneous a day in 6 months
Other Name: preotact
Placebo Comparator: b: placebo 100 ug s.c. inj. once a day
placebo 100 ug sub cutaneous injection once a day
Drug: b:placebo
100 microgram placebo subcutaneous a day for 6 months
Other Name: Placebo

Detailed Description:

Hypoparathyroidism is one of the only hormonal insufficiency states that is usually not treated by replacing the missing hormone. Currently, Standard therapy includes treatment with calcium and an 1alpha-hydroxylated forms of vitamin D (e.g. calcitriol or alphacalcidol) in order to relieve the symptoms associated with hypocalcaemia. However, recent studies have shown that calcium homeostasis can be well regulated by PTH replacement therapy in patients with hypoparathyroidism. It seems that PTH treatment is safe and that it even may posses advantages compared to conventional treatment with vitamin D. As the renal calcium excretion is decreased by PTH therapy, the risk of renal calcifications causing an impaired renal function may be reduced. In addition, some of the hypoparathyroid patients treated with PTH reported less fatigue and increased endurance in response to treatment. This may be due to either a better regulated (i.e. more physiological) calcium homeostasis during PTH therapy, or due to a direct effect of PTH on the neuromuscular system. Therefore, further studies are needed on the effects of PTH replacement in patients with hypoparathyroidism.

Outcome measures:

  • Muscle- and balance function: Effects of treatment on muscle strength and balance function are determined using a dynamometer and a stadiometer (Meititur Ltd, Finland). In addition, effects of treatment on muscle function are assessed through muscle biopsies, electromyographic, echocardiography, and by biochemical measures (muscle enzymes).
  • Quality of life: Effect of treatment on indices of quality of life is assessed using the SF-36v2- and the WHO-Five Well-Being Index (WHO-5)-survey.
  • Calcium homeostasis, bone metabolism, and body composition. Effects of treatment are assessed by measurements of calcitropic hormones, biochemical markers of bone turnover, and iliac crest biopsies. In addition, bone mineral density and body composition is measured.
  Eligibility

Ages Eligible for Study:   25 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • A low endogenous PTH production as verified by low plasma levels of intact PTH, necessitating treatment with 1alpha-hydroxylated vitamin D analogs.
  • At least one years of continuous alphacalcidol, calcitriol, or dihydrotachysterol treatment prior to study entry.
  • Prior to start of study, participants are required to have received a daily supplement of at least 400 IU (10 microgram) of vitamin D (ergocalciferol or cholecalciferol) for at least 3 months or 25hydroxyvitamin D levels above 50 nmol/l. Subjects may be treated with ergocalciferol or cholecalciferol during a run-in period of three months before entering the study.
  • Normal plasma magnesium level (If not, magnesium supplements may be provided during a 3 months run in period).
  • Plasma calcium levels within the normal reference range or slightly below (P-Ca ionized 1.00 to 1.30).
  • Use of safe contraceptive methods (fertile women).
  • Speak and read Danish.

Exclusion Criteria:

  • Known allergic reactions to any of the compounds in the trial medication.
  • Severely impaired renal function (plasma creatinine > 200 micromol/l).
  • Severely impaired hepatic function (Plasma alanine aminotransferase (ALAT) > 100 U/l and/or alkaline phosphatase > 400 U/l).
  • Previous or present malignancies (except a treated skin cancer that is not melanoma or treated carcinoma in situ, 2 years since last therapy).
  • Prior radiation therapy involving the skeleton.
  • Current treatment with raloxifene, calcitonin, systemic corticosteroids above 5 mg a day, fluoride, lithium, PTH, or digoxin.
  • Treatment with anticonvulsant's (within the last 2 years).
  • Immobilization (more than two week within the last 6 months).
  • Granulomatous disease.
  • Paget's disease of bone.
  • Pregnancy / planned within the next year. Hospitalized due to chronic drug or alcohol abuse. Severe malabsorption syndrome.
  • Major medical or social problems that will be likely to preclude participation for one year.
  • Unwillingness to participate.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00730210

Locations
Denmark
Osteoporoseklinikken, Aarhus University Hospital
Aarhus, Jutland, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Investigators
Principal Investigator: Lars Rejnmark, MD,DrMed
Principal Investigator: Tanja Sikjær, MD
  More Information

No publications provided by University of Aarhus

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT00730210     History of Changes
Other Study ID Numbers: EudraCT #008-000606-36)
Study First Received: August 4, 2008
Last Updated: October 23, 2012
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by University of Aarhus:
Hypoparathyroidism
HypoPTH
PTH

Additional relevant MeSH terms:
Hypoparathyroidism
Parathyroid Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 29, 2014