Physiologic Interactions Between the Adrenal- and the Parathyroid Glands

Phase 4

Completed

• Conditions: Osteoporosis; Vitamin D Deficiency; Cardiovascular Disease
• Interventions: Drug: Placebo Valsartan; Drug: Valsartan; Dietary Supplement: Cholecalciferol; Dietary Supplement: Placebo cholecalciferol

• Registration Number: NCT02572960
• Lead Sponsor: University of Aarhus

Brief Summary

To investigate possible physiologic interactions between the adrenal- and the parathyroid glands in patients with secondary hyperparathyroidism.

Detailed Description

In primary hyperparathyroidism, chronic-elevated PTH levels seem to stimulate the renin-angiotensin-aldosterone system (RAAS) which may explain the increased risk of cardiovascular disease. In addition to increased PTH levels, vitamin D has been shown to inhibit the RAAS. However, a possible physiologic interaction needs further investigation.

The purpose of the study is to investigate changes in the RAAS in otherwise healthy postmenopausal women with secondary hyperparathyroidism due to vitamin D deficiency when p-PTH is normalized.

Furthermore, we will evaluate whether an angiotensin 2 receptor blocker can lower PTH in patients with secondary hyperparathyroidism.

Study Timeline

• Study Start: 2015-10
• Study First Submitted: 2015-10-07
• Study First Submitted QC: 2015-10-08
• Study First Posted: 2015-10-09
• Status Verified: 2016-05
• Primary Completion: 2017-05
• Study Completion: 2017-05
• Last Update Submitted: 2018-08-13
• Last Update Posted: 2018-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 81

Inclusion Criteria

• Secondary hyperparathyroidism due to Vitamin D deficiency

Exclusion Criteria

• Cardiovascular disease
• Renal failure
• Liver failure
• Treatment with antihypertensive medication or diuretics
• Treatment with lithium, NSAID or glucocorticoids
• Calcium supplement more than 500 mg per day or Vitamin D supplement more than 25 microgram per day
• Medical treatment for osteoporosis
• Systolic blood pressure below 120 mmHg
• Hypercalcaemia (more than 1,33mmol/L)
• Use of solarium or planned trip to countries, that might increase the endogenous vitamin D synthesis
• Allergic reaction to ACEi or ARBs.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo Valsartan	Placebo cholecalciferol/day for 12 weeks Placebo Valsartan daily for 2 weeks
Placebo	Placebo cholecalciferol	Placebo cholecalciferol/day for 12 weeks Placebo Valsartan daily for 2 weeks
Valsartan	Valsartan	Placebo cholecalciferol/day for 12 weeks Valsartan 80 mg/day for 2 weeks
Cholecalciferol and Valsartan	Valsartan	Cholecalciferol 70 mcg/day for 12 weeks Valsartan 80 mg/day for 2 weeks
Cholecalciferol	Cholecalciferol	Cholecalciferol 70 mcg/day for 12 weeks Placebo Valsartan daily for 2 weeks
Cholecalciferol and Valsartan	Cholecalciferol	Cholecalciferol 70 mcg/day for 12 weeks Valsartan 80 mg/day for 2 weeks

Primary Outcome Measures

Name	Time	Method
Aldosterone, before and after 12 weeks of daily cholecalciferol treatment	Change from baseline p-aldosterone at 12 weeks

Secondary Outcome Measures

Name	Time	Method
Balance as measured by stadiometer (Meitur Ltd)	Change from postural balance at 12 weeks	Postural stability
Muscle strength as measured by isometric tests	Change from baseline isometric muscle strength at 12 weeks	Effects on muscle strength (isometric tests of flexion and extension of thigh and hand), two function-tests (timed up-and go and timed stand-and-sit),
Bone density and geometry as measured by QCT scans	Change from baseline at 12 weeks	Bone quality in spine and hip as assessed by high resolution quantitative computed tomography HRQCT-scans
Quality of Life, SF36	Change from baseline at 12 weeks	SF36v2
Quality of Life, WHO-5	Change from baseline at 12 weeks	WHO-5 well being index
Physical activity	Change from baseline at 12 weeks	Physical activity scale
24 hours arterial stiffness as measured by tonometry	Change from baseline arterial stiffness PWV at 12 weeks	Arteriograph 24
Parathyroid hormone, before and after, daily ARB administrations	Change from baseline p-PTH at 2 weeks
Arterial stiffness	Change from baseline arterial stiffness at 12 weeks	Spygmocor
24 hours blood pressure measured by tonometry	Change from baseline systolic pressure at 12 weeks	Arteriograph 24
Bone density and geometry as measured by HRpQCT scans	Change from baseline at 12 weeks	Bone quality in ankle and forearm as assessed by high resolution peripheral quantitative computed tomography HRpQCT-scans
Bone density by DXA	Change from baseline at 12 weeks	Bone density assessed by dual energy x-ray absorptiometry (DXA)
Electrocardiogram	Change from baseline at 2, 6 and 12 weeks	Hearth rhythm, shortened QT interval, hypertrophy
Hyperparathyroid symptoms	Change from baseline at 12 weeks	Pasieka's parathyroid symptoms score
Biomarkers of calcium- and bone metabolism	Change from baseline at 2, 6 and 12 weeks	Effects of intervention on biochemical markers of calcium and bone metabolism, such as calcium, phosphate, parathyroid hormone, calcitriol, vitamin D-binding protein, bone-specific alkaline phosphatase, osteocalcin, and N-terminal propeptide of type 1 procollagen (P1NP). Also C-terminal telopeptide of type 1 collagen (CTX) and N-telopeptide of type 1 collagen (NTX) among others.

Trial Locations

Locations (1)

Department of Endocrinology and Internal Medicine; 🇩🇰 Aarhus, Denmark