Physiologic Interactions Between the Adrenal- and the Parathyroid Glands (AldOst)

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

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; Vitamin D Deficiency; Osteoporosis
• Intervention / Treatment: Dietary supplement: Cholecalciferol; Drug: Valsartan; Drug: Placebo Valsartan; Dietary supplement: Placebo cholecalciferol

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 Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Department of Endocrinology and Internal Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Lars Rejnmark, Professor, Department of Endocrinology and Internal Medicine

Publications and helpful links

General Publications

• Bislev LS, Wamberg L, Rolighed L, Grove-Laugesen D, Rejnmark L. Effect of Daily Vitamin D3 Supplementation on Muscle Health: An Individual Participant Meta-analysis. J Clin Endocrinol Metab. 2022 Apr 19;107(5):1317-1327. doi: 10.1210/clinem/dgac004.
• Bislev LS, Langagergaard Rodbro L, Rolighed L, Sikjaer T, Rejnmark L. Bone Microstructure in Response to Vitamin D3 Supplementation: A Randomized Placebo-Controlled Trial. Calcif Tissue Int. 2019 Feb;104(2):160-170. doi: 10.1007/s00223-018-0481-6. Epub 2018 Oct 6.
• Bislev LS, Langagergaard Rodbro L, Rolighed L, Sikjaer T, Rejnmark L. Effects of Vitamin D3 Supplementation on Muscle Strength, Mass, and Physical Performance in Women with Vitamin D Insufficiency: A Randomized Placebo-Controlled Trial. Calcif Tissue Int. 2018 Nov;103(5):483-493. doi: 10.1007/s00223-018-0443-z. Epub 2018 Jun 21.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: October 7, 2015
• First Submitted That Met QC Criteria: October 8, 2015
• First Posted (Estimate): October 9, 2015

Study Record Updates

• Last Update Posted (Actual): August 15, 2018
• Last Update Submitted That Met QC Criteria: August 13, 2018
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Nutrition Disorders; Musculoskeletal Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Bone Diseases; Bone Diseases, Metabolic; Cardiovascular Diseases; Vitamin D Deficiency; Osteoporosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Vitamin D; Cholecalciferol; Valsartan
• Other Study ID Numbers: 2014-LSB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No