Disorders of Parathyroid Gland, Hyperparathyroidism
Conditions
Keywords
hyperparathyroidism, vitamin D, ultrasonic ablation, surgery
Brief summary
It is difficulty for the treatment of secondary hyperparathyroidism in the chronic kidney disease (CKD) patients who had not succeeded medical therapy and could not get parathyroidectomy. The investigators suppose that ultrasonic ablation may be a valuable alternative treatment that help control secondary hyperparathyroidism in CKD patients presenting with enlarged parathyroid gland(s) visible at ultrasonography.
Detailed description
Secondary hyperparathyroidism (sHPT) is common in patients with chronic kidney disease (CKD), including those who are undergoing long-term dialysis treatments. sHPT is damaged for bone system, blood system, cardiovascular system, and so on. The treatment of the sHPT of CKD's patient includes dietary phosphate restriction, the use of medicines, and parathyroidectomy. In the mainland of China, there are not certain useful medicines to treat sHPT, including the derivatives of vitamin D, calcimimetic agent, non calcium aluminum phosphate binders. Furthermore, medical therapy is not always successful in achieving adequate control of sHPT. Oral medications have efficacy limitations as well as side-effects. Otherwise, surgery treatment can only be used for the patients with enlarged parathyroid gland(s). The patients may suffer from the injury of operation, hypoparathyroidism, or recurrence of hyperparathyroidism after parathyroidectomy. Then ultrasonic ablation may become a valuable alternative treatment that help control sHPT in selected patients presenting with enlarged parathyroid gland(s) visible at ultrasonography,.
Interventions
PROCEDUREParathyroidectomy
sHPT patients with enlarged glands (≥3)will be randomized into parathyroidectomy group or ultrasonic ablation group. Patients in parathyroidectomy will get parathyroid surgery.
DRUGActive vitamin D
CKD patients suffered from sHPT with 1-3 enlarged gland(s) and without indication of parathyroidectomy will be randomized to oral medicine therapy group or ultrasonic ablation therapy group. Patients in oral medicine group will be treated by active vitamin D and other general treatments, such as dietary phosphate restriction and phosphate binders, according to the suggestions in KDIGO guidelines.
PROCEDUREUltrasonic ablation
CKD-sHPT patients with enlarged parathyroid gland(s) randomized into the ultrasonic ablation group will be treated by ultrasound guided percutaneous parathyroid gland radio frequence ablation. According to the indications of parathyroid surgery, the patients will be divided into two sub-groups. The outcomes of these patients will be compared to the oral medicine group and the parathyroidectomy group, respectively.
Sponsors
Beijing Municipal Science & Technology Commission
Dongliang Zhang, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with age between 18 - 75 years. * Patients with parathyroid nodular or diffuse hyperplasia demonstrated on ultrasound imaging or radioisotope scan. * CKD patients in stage 5, with elevated intact parathyroid hormone (iPTH) levels \> 800pg/mL. * CKD patients have been followed up more than 6 months.
Exclusion criteria
* Primary or Tertiary Hyperparathyroidism (hyperparathyroidism after kidney transplantation). * Patient who underwent total parathyroidectomy and without enlarged parathyroid gland(s). * Known history of parathyroid or other neoplasias in the neck region. * History of neck irradiation. * Major surgery of neck in the last 3 months or other major surgery projected in the subsequent 4 months. * Pregnant or lactating woman. * Patient receiving drugs such as phenobarbital, phenytoin, rifampicin, sucralfate, steroids, flecainide, thioridazine, or most tricyclic antidepressants which could affect vitamin D metabolism. * Treatment with vitamin D derivatives, cinacalcet or other calcimimetics within the past 6 months. * Patients who are currently participating in another clinical trial. * The expected live time is less than 1 year. * Patients suffered from acute myocardial infraction, acute congestive heart failure, or stroke in last 6 months. * Patients whose concurrent illnesses, disability, or geographical residence would hamper attendance at required study visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Achieving the Target on Blood Intact Parathyroid Hormone Level According to Kidney Development Improvement Global Outcome (KDIGO) Guidelines. | 12 months | The blood levels of intact parathyroid hormone (iPTH) will be detected every 3 months for stable patients. The blood test will be more frequent, at least once per-month, after the ultrasonic ablation treatment, surgery, or during the impulse therapy of active vitamin D with large doses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Injury on the Recurrent Laryngeal Nerve (RLN). | 12 months | Comparison of the incidence of RLN injury between ultrasonic ablation group and parathyroidectomy group. |
| Changes of the Blood Levels on Calcium During 12 Months. | Baseline and 12 months | The blood levels of calcium will be detected at least once every 3 months and will be compared to the baseline levels. |
| Changes of Blood Levels on Phosphorus During 12 Months. | Baseline and 12 months | The blood levels of phosphorus will be detected at least once every 3 months and will be compared to the baseline levels. |
| Changes of Blood Levels on iPTH During 12 Months. | Baseline and 12 months | The blood levels of iPTH will be detected at least once every 3 months and will be compared to the baseline levels. |
| Changes of Blood Levels on Bone Specific Alkaline Phosphatase. | Baseline and 12 months | The blood levels of bone specific alkaline phosphatase will be detected at least once every 3 months and will be compared to the baseline levels. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Vitamin D Patients in oral medicine group will be treated by active vitamin D and other general treatments according to the suggestions in KDIGO guidelines.
Active vitamin D: CKD patients suffered from sHPT with 1-3 enlarged gland(s) and without indication of parathyroidectomy will be randomized to oral medicine therapy group or ultrasonic ablation therapy group. Patients in oral medicine group will be treated by active vitamin D and other general treatments, such as dietary phosphate restriction and phosphate binders, according to the suggestions in KDIGO guidelines. | 34 |
| Ultrasonic Ablation Patients in Ultrasonic ablation group will be treated by ultrasound guided percutaneous parathyroid gland radio frequency ablation.
Ultrasonic ablation: CKD-sHPT patients with enlarged parathyroid gland(s) randomized into the ultrasonic ablation group will be treated by ultrasound guided percutaneous parathyroid gland radio frequence ablation. According to the indications of parathyroid surgery, the patients will be divided into two sub-groups. The outcomes of these patients will be compared to the oral medicine group and the parathyroidectomy group, respectively. | 23 |
| Parathyroidectomy Patients in parathyroidectomy group will be treated by parathyroid surgery.
Parathyroidectomy: sHPT patients with enlarged glands (≥3)will be randomized into parathyroidectomy group or ultrasonic ablation group. Patients in parathyroidectomy will get parathyroid surgery. | 22 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 4 | 1 | 0 |
| Overall Study | Physician Decision | 3 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Ultrasonic Ablation | Parathyroidectomy | Active Vitamin D | Total |
|---|---|---|---|---|
| Age, Continuous | 52.0 years | 55.2 years | 56.3 years | 55.3 years |
| BALP-baseline | 18.84 microgram/L STANDARD_DEVIATION 17.94 | 19.27 microgram/L STANDARD_DEVIATION 14.87 | 17.31 microgram/L STANDARD_DEVIATION 6.38 | 17.98 microgram/L STANDARD_DEVIATION 13.32 |
| Ca-baseline | 2.43 mmol/L STANDARD_DEVIATION 0.3 | 2.53 mmol/L STANDARD_DEVIATION 0.23 | 2.31 mmol/L STANDARD_DEVIATION 0.27 | 2.41 mmol/L STANDARD_DEVIATION 0.3 |
| iPTH-baseline | 1550.6 ng/ml STANDARD_DEVIATION 521.7 | 1779.9 ng/ml STANDARD_DEVIATION 514.1 | 239.84 ng/ml STANDARD_DEVIATION 299.01 | 1201.8 ng/ml STANDARD_DEVIATION 498.7 |
| P-baseline | 2.14 mmol/L STANDARD_DEVIATION 0.66 | 2.12 mmol/L STANDARD_DEVIATION 0.45 | 1.95 mmol/L STANDARD_DEVIATION 0.49 | 2.10 mmol/L STANDARD_DEVIATION 0.51 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 23 Participants | 22 Participants | 34 Participants | 79 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 23 participants | 22 participants | 34 participants | 79 participants |
| Sex: Female, Male Female | 12 Participants | 13 Participants | 20 Participants | 45 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 14 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 34 | 5 / 23 | 15 / 22 |
| serious Total, serious adverse events | 1 / 34 | 0 / 23 | 0 / 22 |
Outcome results
Primary
Rate of Achieving the Target on Blood Intact Parathyroid Hormone Level According to Kidney Development Improvement Global Outcome (KDIGO) Guidelines.
The blood levels of intact parathyroid hormone (iPTH) will be detected every 3 months for stable patients. The blood test will be more frequent, at least once per-month, after the ultrasonic ablation treatment, surgery, or during the impulse therapy of active vitamin D with large doses.
Time frame: 12 months
Population: Number of participants analyzed is the number of patients completed study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Vitamin D | Rate of Achieving the Target on Blood Intact Parathyroid Hormone Level According to Kidney Development Improvement Global Outcome (KDIGO) Guidelines. | 30.8 percentage of participants |
| Ultrasonic Ablation | Rate of Achieving the Target on Blood Intact Parathyroid Hormone Level According to Kidney Development Improvement Global Outcome (KDIGO) Guidelines. | 57.1 percentage of participants |
| Parathyroidectomy | Rate of Achieving the Target on Blood Intact Parathyroid Hormone Level According to Kidney Development Improvement Global Outcome (KDIGO) Guidelines. | 90.0 percentage of participants |
Secondary
Changes of Blood Levels on Bone Specific Alkaline Phosphatase.
The blood levels of bone specific alkaline phosphatase will be detected at least once every 3 months and will be compared to the baseline levels.
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Vitamin D | Changes of Blood Levels on Bone Specific Alkaline Phosphatase. | 13.60 microgram/L | Standard Deviation 5.86 |
| Ultrasonic Ablation | Changes of Blood Levels on Bone Specific Alkaline Phosphatase. | 19.48 microgram/L | Standard Deviation 17.33 |
| Parathyroidectomy | Changes of Blood Levels on Bone Specific Alkaline Phosphatase. | 19.20 microgram/L | Standard Deviation 17.95 |
Secondary
Changes of Blood Levels on iPTH During 12 Months.
The blood levels of iPTH will be detected at least once every 3 months and will be compared to the baseline levels.
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Vitamin D | Changes of Blood Levels on iPTH During 12 Months. | 252.2 ng/ml | Standard Deviation 172 |
| Ultrasonic Ablation | Changes of Blood Levels on iPTH During 12 Months. | 372.1 ng/ml | Standard Deviation 253.6 |
| Parathyroidectomy | Changes of Blood Levels on iPTH During 12 Months. | 246.5 ng/ml | Standard Deviation 228.4 |
Secondary
Changes of Blood Levels on Phosphorus During 12 Months.
The blood levels of phosphorus will be detected at least once every 3 months and will be compared to the baseline levels.
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Vitamin D | Changes of Blood Levels on Phosphorus During 12 Months. | 1.91 mmol/L | Standard Deviation 0.41 |
| Ultrasonic Ablation | Changes of Blood Levels on Phosphorus During 12 Months. | 1.51 mmol/L | Standard Deviation 0.29 |
| Parathyroidectomy | Changes of Blood Levels on Phosphorus During 12 Months. | 1.29 mmol/L | Standard Deviation 0.33 |
Secondary
Changes of the Blood Levels on Calcium During 12 Months.
The blood levels of calcium will be detected at least once every 3 months and will be compared to the baseline levels.
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Vitamin D | Changes of the Blood Levels on Calcium During 12 Months. | 2.34 mmol/L | Standard Deviation 0.22 |
| Ultrasonic Ablation | Changes of the Blood Levels on Calcium During 12 Months. | 1.84 mmol/L | Standard Deviation 0.21 |
| Parathyroidectomy | Changes of the Blood Levels on Calcium During 12 Months. | 1.93 mmol/L | Standard Deviation 0.26 |
Secondary
Incidence of Injury on the Recurrent Laryngeal Nerve (RLN).
Comparison of the incidence of RLN injury between ultrasonic ablation group and parathyroidectomy group.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Vitamin D | Incidence of Injury on the Recurrent Laryngeal Nerve (RLN). | 0 participants |
| Ultrasonic Ablation | Incidence of Injury on the Recurrent Laryngeal Nerve (RLN). | 2 participants |