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

Primary Purpose

Hypoparathyroidism

Status

Completed

Phase

Phase 2

Locations

Denmark

Study Type

Interventional

Intervention

a: PTH (1-84)

b:placebo

About this trial

This is an interventional treatment trial for Hypoparathyroidism focused on measuring Hypoparathyroidism, HypoPTH, PTH

Eligibility Criteria

25 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Osteoporoseklinikken, Aarhus University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

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

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

Arm Description

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

placebo 100 ug sub cutaneous injection once a day

Outcomes

Primary Outcome Measures

Increase in maximal voluntary knee extension

Secondary Outcome Measures

Balance function: Is assessed using a stadiometer (Meititur Ltd, Finland)

Effect of treatment on indices of quality of life is assessed using the SF-36v2- and WHO-Five Well-Being Index (WHO-5)-survey.

Effects of treatment on muscle function are assessed through muscle biopsies, electromyographic, and by biochemical measures (muscle enzymes).

Bone mineral density and body composition is measured

Calcium homeostasis and bone metabolism. Effects of treatment are assessed by measurements of calcitropic hormones, biochemical markers of bone turnover, and bone biopsies

Q CT scan of hip and spine

Effects of treatment on diurnal variations of measured biochemical indices, as assessed at the end of the treatment period

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.

Full Information

NCT ID

NCT00730210

First Posted

August 4, 2008

Last Updated

October 23, 2012

Sponsor

University of Aarhus

1. Study Identification

Unique Protocol Identification Number

NCT00730210

Brief Title

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

Acronym

HypoPTH

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2012

Overall Recruitment Status

Completed

Study Start Date

June 2008 (undefined)

Primary Completion Date

August 2010 (Actual)

Study Completion Date

August 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Aarhus

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypoparathyroidism

Keywords

Hypoparathyroidism, HypoPTH, PTH

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

62 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Active Comparator

Arm Description

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

Arm Title

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

Arm Type

Placebo Comparator

Arm Description

placebo 100 ug sub cutaneous injection once a day

Intervention Type

Drug

Intervention Name(s)

a: PTH (1-84)

Other Intervention Name(s)

preotact

Intervention Description

preotact 100 microgram subcutaneous a day in 6 months

Intervention Type

Drug

Intervention Name(s)

b:placebo

Other Intervention Name(s)

Placebo

Intervention Description

100 microgram placebo subcutaneous a day for 6 months

Primary Outcome Measure Information:

Title

Increase in maximal voluntary knee extension

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Balance function: Is assessed using a stadiometer (Meititur Ltd, Finland)

Time Frame

6 months

Title

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

Title

Effects of treatment on muscle function are assessed through muscle biopsies, electromyographic, and by biochemical measures (muscle enzymes).

Time Frame

6 months

Title

Bone mineral density and body composition is measured

Time Frame

6 months

Title

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

Title

Q CT scan of hip and spine

Time Frame

6 months

Title

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

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

25 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lars Rejnmark, MD,DrMed

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Tanja Sikjær, MD

Official's Role

Principal Investigator

Facility Information:

Facility Name

Osteoporoseklinikken, Aarhus University Hospital

City

Aarhus

State/Province

Jutland

ZIP/Postal Code

8000

Country

Denmark

12. IPD Sharing Statement

Citations:

PubMed Identifier

32582855

Citation

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.

Results Reference

derived

PubMed Identifier

25955226

Citation

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.

Results Reference

derived

PubMed Identifier

24687385

Citation

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.

Results Reference

derived

Learn more about this trial

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

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