The Renin-Angiotensin-Aldosterone System and Parathyroid Hormone Control: The RAAS-PARC Study

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01691781
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arm: 1
• Actual Duration (Months): 50
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This study will evaluate whether commonly used blood pressure medications called "ACE inhibitors" can lower parathyroid hormone.

Condition or Disease	Intervention/Treatment	Phase
Hyperparathyroidism	Drug: Lisinopril	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Open Label
• Primary Purpose: Other
• Official Title: The Renin-Angiotensin-Aldosterone System and Parathyroid Hormone Control: The RAAS-PARC Study
• Actual Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: lisinopril Lisinopril - open-label, 2.5-40mg daily	Drug: Lisinopril; Each subject will receive one week of lisinopril and return for repeat for blood measurements.

Outcome Measures

Primary Outcome Measures

1. Parathyroid Hormone Following 1 Week of ACE Inhibitor Administration [1 week]

   PTH values 1 week following ACE inhibitor therapy

Secondary Outcome Measures

1. Urinary Aldosterone Excretion Measurements Following 1 Week of ACE Inhibitor Therapy [1 week]

2. Serum Calcium Following 1 Week of ACE Inhibitor Administration [1 week]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

• Principal Investigator: Anand Vaidya, MD, MMSc, Brigham and Women's Hospital, Harvard Medical School

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anand Vaidya, Principal Investigator, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01691781
• Other Study ID Numbers: 2012p0001961
• First Posted: Sep 25, 2012
• Last Update Posted: Sep 21, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by Anand Vaidya, Principal Investigator, Brigham and Women's Hospital: Hyperparathyroidism; Renin-angiotensin-aldosterone system; ACE inhibitors
• Additional relevant MeSH terms: Hyperparathyroidism; Lisinopril

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Primary Hyperparathyroidism	Normal
Arm/Group Description	Participants with Primary Hyperparathyroidism enrolled to receive open label lisinopril.	Participants without primary hyperparathyroidism enrolled to receive open label lisinopril.
Period Title: Overall Study
STARTED	19	22
COMPLETED	12	15
NOT COMPLETED	7	7

Baseline Characteristics

Arm/Group Title	Primary Hyperparathyroidism	Normals	Total
Arm/Group Description	Participants with Primary Hyperparathyroidism enrolled to receive open label lisinopril.	Participants without primary hyperparathyroidism enrolled to receive open label lisinopril.	Total of all reporting groups
Overall Participants	12	15	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.4 (15.6)	39.6 (12.7)	44.9 (15.3)
Sex: Female, Male (Count of Participants)
Female	5 41.7%	6 40%	11 40.7%
Male	7 58.3%	9 60%	16 59.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 8.3%	1 6.7%	2 7.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 16.7%	6 40%	8 29.6%
White	9 75%	8 53.3%	17 63%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	12 100%	15 100%	27 100%
Parathyroid Hormone at Baseline (pg/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/mL]	79.5 (21.6)	33.3 (25.4)	53.8 (33.0)
Serum calcium (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	10.6 (0.5)	9.4 (0.4)	9.9 (0.7)
Urinary Aldosterone Excretion Rate at baseline (mcg/24 hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mcg/24 hours]	11.7 (18.3)	5.7 (3.5)	8.2 (12.2)

Outcome Measures

1. Primary Outcome

Title	Parathyroid Hormone Following 1 Week of ACE Inhibitor Administration
Description	PTH values 1 week following ACE inhibitor therapy
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Primary Hyperparathyroidism	Normal
Arm/Group Description	Participants with Primary Hyperparathyroidism enrolled to receive open label lisinopril.	Participants without primary hyperparathyroidism enrolled to receive open label lisinopril.
Measure Participants	12	15
Mean (Standard Deviation) [pg/mL]	70.9 (19.6)	32.5 (16.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Primary Hyperparathyroidism
	Comments	The statistical analysis compared the change in PTH, before and after ACE inhibitor therapy, among participants with primary hyperparathyroidism.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.049
	Comments	This p-value reflects the difference in PTH means among participants with primary hyperparathyroidism
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal
	Comments	The statistical analysis compared the change in PTH, before and after ACE inhibitor therapy, among normal control participants (without primary hyperparathyroidism).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments	This p-value reflects the difference in PTH means among normal control participants without primary hyperparathyroidism
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Urinary Aldosterone Excretion Measurements Following 1 Week of ACE Inhibitor Therapy
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Primary Hyperparathyroidism	Normal
Arm/Group Description	Participants with Primary Hyperparathyroidism enrolled to receive open label lisinopril.	Participants without primary hyperparathyroidism enrolled to receive open label lisinopril.
Measure Participants	12	15
Mean (Standard Deviation) [mcg/24 hours]	7.8 (8.9)	6.1 (9.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Primary Hyperparathyroidism
	Comments	The statistical analysis compared the change in urinary aldosterone excretion rate, before and after ACE inhibitor therapy, among participants with primary hyperparathyroidism.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments	This p-value reflects the comparison of means among the primary hyperparathyroidism group only.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal
	Comments	The statistical analysis compared the change in urinary aldosterone excretion rate, before and after ACE inhibitor therapy, among normal control participants without primary hyperparathyroidism.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments	This p-value reflects the mean difference in 24h aldosterone excretion rate among normal control participants without primary hyperparathyroidism
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Serum Calcium Following 1 Week of ACE Inhibitor Administration
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Primary Hyperparathyroidism	Normal
Arm/Group Description	Participants with Primary Hyperparathyroidism enrolled to receive open label lisinopril.	Participants without primary hyperparathyroidism enrolled to receive open label lisinopril.
Measure Participants	12	15
Mean (Standard Deviation) [mg/dL]	10.5 (0.4)	9.5 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Primary Hyperparathyroidism
	Comments	The statistical analysis compared the change in serum calcium, before and after ACE inhibitor therapy, among participants with primary hyperparathyroidism.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments	This p-value reflects the statistic for the comparison of mean calcium levels for the primary hyperparathyroidism group.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal
	Comments	The statistical analysis compared the change in serum calcium, before and after ACE inhibitor therapy, among normal control participants without primary hyperparathyroidism.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments	This p-value reflects the statistic for the comparison of mean calcium levels for the normal control participants without primary hyperparathyroidism.
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	4 years
Arm/Group Title	Primary Hyperparathyroidism		Normal
Arm/Group Description	Participants with Primary Hyperparathyroidism enrolled to receive open label lisinopril.		Participants without primary hyperparathyroidism enrolled to receive open label lisinopril.
All Cause Mortality
	Primary Hyperparathyroidism		Normal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/15 (0%)
Serious Adverse Events
	Primary Hyperparathyroidism		Normal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Primary Hyperparathyroidism		Normal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)		1/15 (6.7%)
Gastrointestinal disorders
diarrhea	0/12 (0%)	0	1/15 (6.7%)	1
General disorders
Weakness	1/12 (8.3%)	1	0/15 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/12 (8.3%)	1	0/15 (0%)	0

Limitations/Caveats

This a small physiology pilot study that is open-label and non-randomized. The intervention was an ACE inhibitor, an approved therapy. Results have physiologic implications, but treatment implications are not intended.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.