Primary Hyperparathyroidism: Short-term Calcimimetics Treatment - Relevance for Parathyroid Surgery Decisions?

Study Overview
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Brief Summary
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Patients with primary hyperparathyroidism (pHPT) often present with fatigue, psychological and cognitive symptoms. Improvement in these symptoms after parathyroid adenomectomy (PTX) has been reported. But physicians lack a method to attribute the symptoms to pHPT and to predict the reversibility after PTX. This study aims to evaluate short-term calcimimetic treatment as a tool for predicting the outcome of PTX on muscle strength, quality of life, psychological symptoms, and cognitive function in patients with pHPT. Material and Methods: 118 patients scheduled for PTX at Karolinska University Hospital, Sweden, will have a four week treatment with calcimimetics (Mimpara®) before undergoing surgery. Biochemicals, muscle strength, quality of life, psychological symptoms and cognitive function will be analysed at baseline, after four week follow-up and postoperatively. Hypothesis: The outcome of short-term calcimimetic treatment can predict the outcome of PTX on muscle strength, quality of life, psychological symptoms, and cognitive function in patients with pHPT

Detailed Description
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The study evaluates if short-term treatment with calcimimetics may be used for patients with PHPT as a relevant guide in the decision of when to choose parathyroid surgery, by predicting the outcome of surgical treatment. 120 ± 2 patients with primary hyperparathyroidism scheduled for parathyroid surgery will be included in the study after informed consent and will receive study medication with cinacalcet, Mimpara® 30 mgx1 for four weeks. In case of persistent hypercalcemia after two weeks of treatment with Mimpara® 30 mgx1, the dosage of Mimpara® will be increased to 60 mg daily. During the study drug treatment period, the patients will be followed closely at least once a week with clinical monitoring and control of serum ionized calcium, given the risk of side effects and hypocalcemia. If the concentration of ionized calcium in serum will decrease to a subnormal level (<1.15 mmol/l), the Mimpara® treatment will be discontinued temporarily and only reinserted in a lower dose (30 mg x 1) if the concentration of ionized calcium raises over 1.33 mmol/l. The size of the cohort has been decided after power estimations based on the results in study part A. Both groups will go through the test panel of self-rating scales described above at four occasions (Figure). The Outcome to be registered are the changes from baseline to the end of the study medication period compared to the changes postoperatively, thus the changes between the Visit 2 to Visit 6 and the changes between Visit 2 and Visit 7 and Visit 8 respektively. Assessments and Procedures Visit 1: Clinical examination (general condition, neck, blood pressure, cor et pulm). Screening of patients with primary hyperparathyroidism scheduled for parathyroid surgery. Patient that fulfills inclusion and exclusion criteria will be asked to participate in the study. Visit 2: Informed consent is signed. Test panel of self rating scales (Quality of Life Questionnaire-Core 30 (QLQ-C30), Positive States of Mind (PSOM )and Hospital Anxiety and Depression scale (HAD), cognitive test (Montreal cognitive assessment (MoCA-Test)) and muscle strength (Timed stand test). Blood samples are drawn within 2 weeks before and analyzed for: parathyroid hormone (p-PTH), s-ionized calcium, p-total calcium, p-albumin, p-creatinine, p-phosphate, s-25-OH-D-vitamin and p-TSH. Initiation of treatment with Mimpara® 30 mg x 1. Clinical examination (general condition, blood pressure). For fertile women, a pregnancy test is demanded before enrollment. Visit 3: Week 1 (± 2 days); blood samples for analysis of ionized calcium. History of symptoms related to hypocalcemia (paresthesias, cramps, muscle fatigue). Clinical examination when indicated (general condition, blood pressure). Visit 4: Week 2 (± 2 days); blood samples for analysis of ionized calcium. History as above. Mimpara® continued, If the ionized calcium level is >1.33 mmol/l: increase of dosage of Mimpara® to 30 mg x 2. Visit 5: Week 3 (± 2 days); blood samples for analysis of ionized calcium. History as above. Mimpara® treatment completed. Visit 6 (3): Week 4 (± 2 weeks in study B); Test panel of self rating scales (QLQ-C30, PSOM and HAD), cognitive test (MoCA-Test) and muscle strength (Timed stand test). Blood samples are drawn and analyzed for: plasma (p)-PTH, serum(s)-ionized serum calcium, p-total calcium, p-albumin, p-creatinine, p-phosphate. Visit 7 (4): Postoperative follow up, 6 (± 1 week) post surgery; Test panel of self rating scales (QLQ-C30, PSOM and HAD), cognitive test (MoCA-Test) and muscle strength (Timed stand test). Blood samples are drawn and analyzed for plasma p-PTH, s-ionized calcium, p-total calcium, p-albumin, p-creatinine, p-phosphate, s-25-OH-D-vitamin and p-TSH. Visit 8 (5): Postoperatively, 6 months post surgery (± 3 weeks); Test panel of self rating scales (QLQ-C30, PSOM and HAD), cognitive test (MoCA-Test) and muscle strength (Timed stand test). Blood samples are drawn and analyzed for plasma (p)-PTH, s-ionized calcium, p-total calcium, p-albumin, p-creatinine, p-phosphate, s-25-OH-D-vitamin and p-TSH.

Official Title
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Primary Hyperparathyroidism: Short-term Calcimimetics Treatment - Relevance for Parathyroid Surgery Decisions?

Conditions
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Primary Hyperparathyroidism

Intervention / Treatment
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* Drug: Cinacalcet
* Procedure: parathyroid adenomectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary hyperparathyroidism Scheduled for parathyroid surgery Age >40 Ability to participate in all tests included in the study model Signed consent Exclusion Criteria: Pregnancy Breast feeding Fertile woman not using contraceptives (IUD or pills) Impaired kidney function, GFR < 40 ml/min Intolerance to Mimpara® Previously treated with Mimpara® Participating in other ongoing clinical study Epilepsy Severe hepatic impairment Hypotension Heart failure (NYHA class 3-4, symptoms with minimal exertion) Medication with ketoconazole (oral) or tricyclic antidepressants

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

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: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cinacalcet<br>Cinacalcet, Mimpara®: 30 mgx1 for four weeks. In case of persistent hypercalcemia after two weeks of treatment with Mimpara® 30 mgx1, the dosage of Mimpara® will be increased to 60 mg daily. Second intervention: Parathyroid adenomectomy. | Drug: Cinacalcet<br>* Cinacalcet, Mimpara® 30mgx1-2 for 4 weeks<br>* Other names: Mimpara®;Procedure: parathyroid adenomectomy<br>* surgical removal of pathologic parathyroid tissue<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predictive outcome in Quality of Life after parathyroidectomy | Health related quality of life measured by EORTC QLQ-C30 (total score) | after four weeks of calcimimetic treatment and postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychological well-being | Psychological well-being, evaluated with the validated form Positive States of Mind, PSOM | After four weeks of calcimimetic treatment and postoperatively | 
| Anxiety and depression | Depression and anxiety; evaluated with the Hospital Anxiety and Depression (HAD) scale | After four weeks of calcimimetic treatment and postoperatively | 
| Muscle strength | Leg muscle strength measured by Timed stand-test (repeated uprise from chair) | After four weeks of calcimimetic treatment and postoperatively | 
| Biochemical data | AE/SAE recording and safety blood samples; serum levels of p-PTH, s-ionized calcium, p-total calcium, p-albumin, p-creatinine, p-phosphate, s-25-OH-D and thyroid-stimulating hormone (TSH) | After four weeks of calcimimetic treatment and postoperatively | 
| Cognitive function | Cognitive function evaluated with Montreal cognitive assessment (MoCA-test) | after four weeks of calcimimetic treatment and postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary hyperparathyroidism, Calcimimetic Agents, Parathyroid adenomectomy