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

August 5, 2024 updated by: Inga-Lena Nilsson, Karolinska University Hospital

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

110

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Stockholm, Sweden, 171 76
        • Karolinska University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cinacalcet

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
Cinacalcet, Mimpara® 30mgx1-2 for 4 weeks
Other Names:
  • Mimpara®
  • H05BX01
Procedure: parathyroid adenomectomy
surgical removal of pathologic parathyroid tissue

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Predictive outcome in Quality of Life after parathyroidectomy
Time Frame: after four weeks of calcimimetic treatment and postoperatively
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
Time Frame: After four weeks of calcimimetic treatment and postoperatively
Psychological well-being, evaluated with the validated form Positive States of Mind, PSOM
After four weeks of calcimimetic treatment and postoperatively
Anxiety and depression
Time Frame: After four weeks of calcimimetic treatment and postoperatively
Depression and anxiety; evaluated with the Hospital Anxiety and Depression (HAD) scale
After four weeks of calcimimetic treatment and postoperatively
Muscle strength
Time Frame: After four weeks of calcimimetic treatment and postoperatively
Leg muscle strength measured by Timed stand-test (repeated uprise from chair)
After four weeks of calcimimetic treatment and postoperatively
Biochemical data
Time Frame: After four weeks of calcimimetic treatment and postoperatively
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
Time Frame: after four weeks of calcimimetic treatment and postoperatively
Cognitive function evaluated with Montreal cognitive assessment (MoCA-test)
after four weeks of calcimimetic treatment and postoperatively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska University Hospital

Collaborators

Karolinska Institutet

Investigators

  • Principal Investigator: Inga-Lena Nilsson, M.D., Ph.D, Karolinska UH
  • Principal Investigator: Inga-Lena Y Nilsson, MD, PhD, Karolinska UH

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2014

Primary Completion (Actual)

December 1, 2021

Study Completion (Actual)

December 31, 2021

Study Registration Dates

First Submitted

August 17, 2014

First Submitted That Met QC Criteria

August 27, 2014

First Posted (Estimated)

August 28, 2014

Study Record Updates

Last Update Posted (Actual)

August 6, 2024

Last Update Submitted That Met QC Criteria

August 5, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2012-005374-57

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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