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

Primary Hyperparathyroidism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02227264
• Other study ID #: 2012-005374-57
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 2014
• Est. completion date: December 2021

Study information

• Verified date: January 2020
• Source: Karolinska University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 123
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hyperparathyroidism
• Hyperparathyroidism, Primary
• Primary Hyperparathyroidism

Intervention

Drug:
• Cinacalcet
Cinacalcet, Mimpara® 30mgx1-2 for 4 weeks

Procedure:
• parathyroid adenomectomy
surgical removal of pathologic parathyroid tissue

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital	Stockholm

Sponsors (2)

Lead Sponsor	Collaborator
Karolinska University Hospital	Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Psychological well-being	Psychological well-being, evaluated with the validated form Positive States of Mind, PSOM	After four weeks of calcimimetic treatment and postoperatively
Secondary	Anxiety and depression	Depression and anxiety; evaluated with the Hospital Anxiety and Depression (HAD) scale	After four weeks of calcimimetic treatment and postoperatively
Secondary	Muscle strength	Leg muscle strength measured by Timed stand-test (repeated uprise from chair)	After four weeks of calcimimetic treatment and postoperatively
Secondary	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
Secondary	Cognitive function	Cognitive function evaluated with Montreal cognitive assessment (MoCA-test)	after four weeks of calcimimetic treatment and postoperatively

External Links

•   Ethical Review Board
•   Karolinska Institute
•   Karolinska University Hospital