Physiologic Interactions Between the Adrenal- and the Parathyroid Glands

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

Detailed Description
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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.

Official Title
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Physiologic Interactions Between the Adrenal- and the Parathyroid Glands

Conditions
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Osteoporosis, Vitamin D Deficiency, Cardiovascular Disease

Intervention / Treatment
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* Drug: Valsartan
* Drug: Placebo Valsartan
* Dietary Supplement: Cholecalciferol
* Dietary Supplement: Placebo cholecalciferol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Cholecalciferol<br>Cholecalciferol 70 mcg/day for 12 weeks Placebo Valsartan daily for 2 weeks | Dietary Supplement: Cholecalciferol<br>* 12 weeks of daily cholecalciferol treatment, 70 microgram per day<br>* Other names: Vitamin D3;|
| Active Comparator: Valsartan<br>Placebo cholecalciferol/day for 12 weeks Valsartan 80 mg/day for 2 weeks | Drug: Valsartan<br>* 2 weeks of Valsartan 80 mg per day<br>|
| Placebo Comparator: Placebo<br>Placebo cholecalciferol/day for 12 weeks Placebo Valsartan daily for 2 weeks | Drug: Placebo Valsartan<br>* 2 weeks of Placebo Valsartan, one tablet per day. Placebo tablets are identical in regards to size and appearance to the experimental intervention tablet.<br>Dietary Supplement: Placebo cholecalciferol<br>* 12 weeks of daily Placebo cholecalciferol treatment. Placebo tablets are identical in regards to size and appearance to the experimental intervention tablet.<br>* Other names: Placebo D3;|
| Active Comparator: Cholecalciferol and Valsartan<br>Cholecalciferol 70 mcg/day for 12 weeks Valsartan 80 mg/day for 2 weeks | Drug: Valsartan<br>* 2 weeks of Valsartan 80 mg per day<br>Dietary Supplement: Cholecalciferol<br>* 12 weeks of daily cholecalciferol treatment, 70 microgram per day<br>* Other names: Vitamin D3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aldosterone, before and after 12 weeks of daily cholecalciferol treatment |  | Change from baseline p-aldosterone at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parathyroid hormone, before and after, daily ARB administrations |  | Change from baseline p-PTH at 2 weeks | 
| Arterial stiffness | Spygmocor | Change from baseline arterial stiffness at 12 weeks | 
| 24 hours arterial stiffness as measured by tonometry | Arteriograph 24 | Change from baseline arterial stiffness PWV at 12 weeks | 
| 24 hours blood pressure measured by tonometry | Arteriograph 24 | Change from baseline systolic pressure at 12 weeks | 
| Balance as measured by stadiometer (Meitur Ltd) | Postural stability | Change from postural balance at 12 weeks | 
| Muscle strength as measured by isometric tests | 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), | Change from baseline isometric muscle strength at 12 weeks | 
| Bone density and geometry as measured by QCT scans | Bone quality in spine and hip as assessed by high resolution quantitative computed tomography HRQCT-scans | Change from baseline at 12 weeks | 
| Bone density and geometry as measured by HRpQCT scans | Bone quality in ankle and forearm as assessed by high resolution peripheral quantitative computed tomography HRpQCT-scans | Change from baseline at 12 weeks | 
| Bone density by DXA | Bone density assessed by dual energy x-ray absorptiometry (DXA) | Change from baseline at 12 weeks | 
| Electrocardiogram | Hearth rhythm, shortened QT interval, hypertrophy | Change from baseline at 2, 6 and 12 weeks | 
| Biomarkers of calcium- and bone metabolism | 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. | Change from baseline at 2, 6 and 12 weeks | 
| Quality of Life, SF36 | SF36v2 | Change from baseline at 12 weeks | 
| Quality of Life, WHO-5 | WHO-5 well being index | Change from baseline at 12 weeks | 
| Physical activity | Physical activity scale | Change from baseline at 12 weeks | 
| Hyperparathyroid symptoms | Pasieka's parathyroid symptoms score | Change from baseline at 12 weeks |