Hyperparathyroidism
Conditions
Keywords
Hyperparathyroidism, Renin-angiotensin-aldosterone system, ACE inhibitors
Brief summary
This study will evaluate whether commonly used blood pressure medications called ACE inhibitors can lower parathyroid hormone.
Detailed description
The RAAS-PARC study will evaluate whether angiotensin-converting enzyme inhibitors (ACEi) can lower parathyroid hormone (PTH) in normal controls and in individuals have a diagnosis of primary hyperparathyroidism. Emerging data has implicated the renin-angiotensin-aldosterone system (RAAS) activity with increased PTH. The principal investigator, and other investigators, have previously shown that inhibiting the RAAS may lower PTH. The current study will focus on: 1. Normal Physiology: Does an ACEi (which lowers angiotensin II and aldosterone) reduce PTH in normal individuals? 2. Pathophysiology: Does an ACEi reduce PTH in individuals with primary hyperparathyroidism? The results of this study may have important implications for cardiovascular and skeletal health, as both the RAAS and PTH have been implicated as mediators of these conditions.
Interventions
DRUGLisinopril
Each subject will receive one week of lisinopril and return for repeat for blood measurements.
Sponsors
Brigham and Women's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy subjects with with no medical problems (n=15) and individuals with primary hyperparathyroidism (n=30) * normal blood pressure or stage 1 hypertension that is either untreated, or adequately treated with a single anti-hypertensive medication. * Age \>18 years and \<80 years * Estimated GFR \> 60ml/min
Exclusion criteria
* Chronic Kidney Disease or eGFR\<60 * Stage 2 or Stage 3 hypertension or the use of more than 1 antihypertensive drug * Type 2 Diabetes Mellitus that is not controlled by diet or Metformin alone or with a Hemoglobin A1c \>7.5% * History of liver failure * History of heart failure * The use of typical or atypical antipsychotic medications or lithium. * Chronic inflammatory conditions (such as inflammatory bowel disease or arthritis) that are treated with prescribed doses of NSAIDs or glucocorticoids * The use of prescribed doses of potassium supplements. * Illness requiring overnight hospitalization in the past 6 months * Active tobacco or recreational drug use * Pregnancy or current breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parathyroid Hormone Following 1 Week of ACE Inhibitor Administration | 1 week | PTH values 1 week following ACE inhibitor therapy |
Secondary
| Measure | Time frame |
|---|---|
| Urinary Aldosterone Excretion Measurements Following 1 Week of ACE Inhibitor Therapy | 1 week |
| Serum Calcium Following 1 Week of ACE Inhibitor Administration | 1 week |
Countries
United States
Participant flow
Pre-assignment details
All enrolled participants had to undergo a washout of ACE inhibitors (if applicable) during which time their blood pressure had to remain within safety parameters, and they had to complete a controlled sodium diet.
Participants by arm
| Arm | Count |
|---|---|
| Primary Hyperparathyroidism Participants with Primary Hyperparathyroidism enrolled to receive open label lisinopril. | 12 |
| Normals Participants without primary hyperparathyroidism enrolled to receive open label lisinopril. | 15 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Normals | Total | Primary Hyperparathyroidism |
|---|---|---|---|
| Age, Continuous | 39.6 years STANDARD_DEVIATION 12.7 | 44.9 years STANDARD_DEVIATION 15.3 | 51.4 years STANDARD_DEVIATION 15.6 |
| Parathyroid Hormone at Baseline | 33.3 pg/mL STANDARD_DEVIATION 25.4 | 53.8 pg/mL STANDARD_DEVIATION 33 | 79.5 pg/mL STANDARD_DEVIATION 21.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 8 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 17 Participants | 9 Participants |
| Region of Enrollment United States | 15 Participants | 27 Participants | 12 Participants |
| Serum calcium | 9.4 mg/dL STANDARD_DEVIATION 0.4 | 9.9 mg/dL STANDARD_DEVIATION 0.7 | 10.6 mg/dL STANDARD_DEVIATION 0.5 |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 5 Participants |
| Sex: Female, Male Male | 9 Participants | 16 Participants | 7 Participants |
| Urinary Aldosterone Excretion Rate at baseline | 5.7 mcg/24 hours STANDARD_DEVIATION 3.5 | 8.2 mcg/24 hours STANDARD_DEVIATION 12.2 | 11.7 mcg/24 hours STANDARD_DEVIATION 18.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 15 |
| other Total, other adverse events | 2 / 12 | 1 / 15 |
| serious Total, serious adverse events | 0 / 12 | 0 / 15 |
Outcome results
Primary
Parathyroid Hormone Following 1 Week of ACE Inhibitor Administration
PTH values 1 week following ACE inhibitor therapy
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Hyperparathyroidism | Parathyroid Hormone Following 1 Week of ACE Inhibitor Administration | 70.9 pg/mL | Standard Deviation 19.6 |
| Normal | Parathyroid Hormone Following 1 Week of ACE Inhibitor Administration | 32.5 pg/mL | Standard Deviation 16.7 |
Comparison: The statistical analysis compared the change in PTH, before and after ACE inhibitor therapy, among participants with primary hyperparathyroidism.p-value: 0.049t-test, 2 sided
Comparison: The statistical analysis compared the change in PTH, before and after ACE inhibitor therapy, among normal control participants (without primary hyperparathyroidism).p-value: 0.8t-test, 2 sided
Secondary
Serum Calcium Following 1 Week of ACE Inhibitor Administration
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Hyperparathyroidism | Serum Calcium Following 1 Week of ACE Inhibitor Administration | 10.5 mg/dL | Standard Deviation 0.4 |
| Normal | Serum Calcium Following 1 Week of ACE Inhibitor Administration | 9.5 mg/dL | Standard Deviation 0.3 |
Comparison: The statistical analysis compared the change in serum calcium, before and after ACE inhibitor therapy, among participants with primary hyperparathyroidism.p-value: 0.48t-test, 2 sided
Comparison: The statistical analysis compared the change in serum calcium, before and after ACE inhibitor therapy, among normal control participants without primary hyperparathyroidism.p-value: 0.8t-test, 2 sided
Secondary
Urinary Aldosterone Excretion Measurements Following 1 Week of ACE Inhibitor Therapy
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Hyperparathyroidism | Urinary Aldosterone Excretion Measurements Following 1 Week of ACE Inhibitor Therapy | 7.8 mcg/24 hours | Standard Deviation 8.9 |
| Normal | Urinary Aldosterone Excretion Measurements Following 1 Week of ACE Inhibitor Therapy | 6.1 mcg/24 hours | Standard Deviation 9.1 |
Comparison: The statistical analysis compared the change in urinary aldosterone excretion rate, before and after ACE inhibitor therapy, among participants with primary hyperparathyroidism.p-value: 0.22t-test, 2 sided
Comparison: The statistical analysis compared the change in urinary aldosterone excretion rate, before and after ACE inhibitor therapy, among normal control participants without primary hyperparathyroidism.p-value: 0.86t-test, 2 sided