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

NCT ID: NCT00730210

Last Updated: 2012-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2010-08-31

Brief Summary

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.

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.

Conditions

Hypoparathyroidism

Keywords

Hypoparathyroidism; HypoPTH; PTH

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

a: PTH (1-84) 100 ug s.c.inj. once a day

PTH (1-84) 100 ug subcutaneous injections once a day

Group Type: ACTIVE_COMPARATOR

a: PTH (1-84)

Intervention Type: DRUG

preotact 100 microgram subcutaneous a day in 6 months

b: placebo 100 ug s.c. inj. once a day

placebo 100 ug sub cutaneous injection once a day

Group Type: PLACEBO_COMPARATOR

b:placebo

Intervention Type: DRUG

100 microgram placebo subcutaneous a day for 6 months

Interventions

a: PTH (1-84)

preotact 100 microgram subcutaneous a day in 6 months

Intervention Type: DRUG

b:placebo

100 microgram placebo subcutaneous a day for 6 months

Intervention Type: DRUG

Other Intervention Names

preotact; Placebo

Eligibility 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.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lars Rejnmark, MD,DrMed

Role: PRINCIPAL_INVESTIGATOR

Tanja Sikjær, MD

Role: PRINCIPAL_INVESTIGATOR

Locations

Osteoporoseklinikken, Aarhus University Hospital

Aarhus, Jutland, Denmark

Countries

Denmark

References

Grunewald TA, Liebi M, Wittig NK, Johannes A, Sikjaer T, Rejnmark L, Gao Z, Rosenthal M, Guizar-Sicairos M, Birkedal H, Burghammer M. Mapping the 3D orientation of nanocrystals and nanostructures in human bone: Indications of novel structural features. Sci Adv. 2020 Jun 12;6(24):eaba4171. doi: 10.1126/sciadv.aba4171. eCollection 2020 Jun.

Reference Type: DERIVED

PMID: 32582855 (View on PubMed)

Harslof T, Sikjaer T, Sorensen L, Pedersen SB, Mosekilde L, Langdahl BL, Rejnmark L. The Effect of Treatment With PTH on Undercarboxylated Osteocalcin and Energy Metabolism in Hypoparathyroidism. J Clin Endocrinol Metab. 2015 Jul;100(7):2758-62. doi: 10.1210/jc.2015-1477. Epub 2015 May 8.

Reference Type: DERIVED

PMID: 25955226 (View on PubMed)

Sikjaer T, Rolighed L, Hess A, Fuglsang-Frederiksen A, Mosekilde L, Rejnmark L. Effects of PTH(1-84) therapy on muscle function and quality of life in hypoparathyroidism: results from a randomized controlled trial. Osteoporos Int. 2014 Jun;25(6):1717-26. doi: 10.1007/s00198-014-2677-6. Epub 2014 Apr 1.

Reference Type: DERIVED

PMID: 24687385 (View on PubMed)

Other Identifiers

EudraCT #008-000606-36)

Identifier Type: -

Identifier Source: org_study_id