Trial Outcomes & Findings for Metabolic Effects of Natriuretic Peptide Hormones (NCT NCT03397966)
NCT ID: NCT03397966
Last Updated: 2024-11-25
Results Overview
At each visit (Study Visits 1 and 2), resting energy expenditure (EE) will be determined by indirect calorimetry, using a metabolic cart. Energy expenditure will be measured at baseline (just prior to the infusion) and during the 240-minute intravenous infusion at Study Visits 1 and 2. The primary endpoint will be change in resting energy expenditure, calculated as final resting energy expenditure (at end of 240-minute infusion) adjusted for baseline value.
TERMINATED
PHASE4
5 participants
At baseline and at end of 240-minute IV infusion (at each study visit). (At Study Visit 1 and 2, EE will be assessed at baseline and at end of 240-minute intravenous infusion. Visits will be separated by at least 14 days.)
2024-11-25
Participant Flow
Enrolled subjects underwent a screening visit to determine eligibility for the study. The screening visit included a medical history, physical examination, and a blood draw for CMP, CBC, HbA1c, TSH, and free T4. A pregnancy test was completed on female subjects of child-bearing potential. Eligible subjects who still wished to participate in the study were then enrolled for the main study visits.
Participant milestones
| Measure |
BNP Followed by Placebo (Control)
At study visit 1, subjects will receive an IV infusion of recombinant human b-type natriuretic peptide (BNP (1-32)) for 240 minutes (at a rate of 10 ng/kg/minute, preceded by IV bolus of 100 ng/kg).
After a washout of a minimum of 2 weeks, subjects will present for Study Visit 2, where they will receive an IV infusion of placebo control (normal saline) for 240 minutes.
|
Placebo (Control) Followed by BNP
At study visit 1, subjects will receive an IV infusion of placebo (normal saline).
After a washout of a minimum of 2 weeks, subjects will present for Study Visit 2, where they will receive an IV infusion of recombinant human b-type natriuretic peptide (BNP (1-32)) for 240 minutes (at a rate of 10 ng/kg/ minute, preceded by IV bolus of 100 ng/kg).
|
|---|---|---|
|
Study Visit 1
STARTED
|
3
|
2
|
|
Study Visit 1
COMPLETED
|
3
|
2
|
|
Study Visit 1
NOT COMPLETED
|
0
|
0
|
|
Washout Period (2+ Weeks)
STARTED
|
3
|
2
|
|
Washout Period (2+ Weeks)
COMPLETED
|
3
|
2
|
|
Washout Period (2+ Weeks)
NOT COMPLETED
|
0
|
0
|
|
Study Visit 2
STARTED
|
3
|
2
|
|
Study Visit 2
COMPLETED
|
3
|
2
|
|
Study Visit 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Metabolic Effects of Natriuretic Peptide Hormones
Baseline characteristics by cohort
| Measure |
BNP Followed by Placebo
n=3 Participants
At study visit 1, subjects will receive an IV infusion of recombinant human b-type natriuretic peptide (BNP (1-32)) for 240 minutes (at a rate of 10 ng/kg/minute, preceded by IV bolus of 100 ng/kg).
After a washout of a minimum of 2 weeks, subjects will present for Study Visit 2, where they will receive an IV infusion of placebo control (normal saline) for 240 minutes.
|
Placebo Followed by BNP
n=2 Participants
At study visit 1, subjects will receive an IV infusion of placebo (normal saline).
After a washout of a minimum of 2 weeks, subjects will present for Study Visit 2, where they will receive an IV infusion of recombinant human b-type natriuretic peptide (BNP (1-32)) for 240 minutes (at a rate of 10 ng/kg/minute, preceded by IV bolus of 100 ng/kg).
|
Total
n=5 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
36 years
n=5 Participants
|
34.5 years
n=7 Participants
|
36 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At baseline and at end of 240-minute IV infusion (at each study visit). (At Study Visit 1 and 2, EE will be assessed at baseline and at end of 240-minute intravenous infusion. Visits will be separated by at least 14 days.)Population: All participants who received both interventions and completed all study visits are included in the analysis.
At each visit (Study Visits 1 and 2), resting energy expenditure (EE) will be determined by indirect calorimetry, using a metabolic cart. Energy expenditure will be measured at baseline (just prior to the infusion) and during the 240-minute intravenous infusion at Study Visits 1 and 2. The primary endpoint will be change in resting energy expenditure, calculated as final resting energy expenditure (at end of 240-minute infusion) adjusted for baseline value.
Outcome measures
| Measure |
BNP Infusion
n=5 Participants
Participants who received BNP infusion at either Study Visit 1 or Study Visit 2.
|
Placebo (Control)
n=5 Participants
Participants who received placebo (normal saline) infusion at either Study Visit 1 or Study Visit 2.
|
|---|---|---|
|
Change in Resting Energy Expenditure (EE)
REE at baseline
|
1867 kcal/day
Interval 1649.0 to 1959.0
|
1800 kcal/day
Interval 1769.0 to 2020.0
|
|
Change in Resting Energy Expenditure (EE)
REE at end of infusion
|
1970 kcal/day
Interval 1687.0 to 1998.0
|
1883 kcal/day
Interval 1782.0 to 1926.0
|
SECONDARY outcome
Timeframe: A subcutaneous biopsy will be collected after the end of 240-minute IV infusion, at both Study Visits 1 and 2 (Visits will be separated by at least 14 days.)Population: All participants (N= 4) who had paired adipose tissue samples available (who had adipose tissue sample collected after both the BNP infusion and after the placebo infusion). There was 1 subject who did not have adipose tissue collected at one of the study visits, and thus is not included in the statistical analysis.
Subcutaneous adipose tissue biopsies will be obtained after the conclusion of the 240-minute IV infusion at Study Visits 1 and 2. These tissues will be analyzed for adipose tissue gene expression. The adipose tissue gene expression after the BNP infusion will be compared to expression after the placebo infusion. Units are relative UCP1 gene expression (quantified using quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR)), normalized to a housekeeping gene).
Outcome measures
| Measure |
BNP Infusion
n=4 Participants
Participants who received BNP infusion at either Study Visit 1 or Study Visit 2.
|
Placebo (Control)
n=4 Participants
Participants who received placebo (normal saline) infusion at either Study Visit 1 or Study Visit 2.
|
|---|---|---|
|
Adipose Tissue Gene Expression of Uncoupling Protein 1 (UCP1)
|
9.66 fold change
Standard Error 3.42
|
3.30 fold change
Standard Error 1.18
|
Adverse Events
BNP Followed by Normal Saline (Control)
Normal Saline (Control) Followed by BNP
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
BNP Followed by Normal Saline (Control)
n=5 participants at risk
Subjects will initially receive an IV infusion of recombinant human b-type natriuretic peptide (BNP (1-32)) for 240 minutes. After a wash out of a minimum of 2 weeks subject will receive an IV infusion of normal saline for 240 minutes.
recombinant human BNP (1-32): Subjects will receive an IV infusion of recombinant human BNP1-32 (6 mcg BNP/ml saline) for 240 minutes.
normal saline (placebo): Subjects will receive an IV infusion of normal saline for 240 minutes. The volume of saline delivered will be equivalent to the volume of saline that the subject receives during the BNP infusion visit.
|
Normal Saline (Control) Followed by BNP
n=5 participants at risk
Subjects will initially receive an IV infusion of normal saline for 240 minutes. After a wash out of a minimum of 2 weeks subject will receive an IV infusion of recombinant human b-type natriuretic peptide (BNP (1-32)) for 240 minutes. The volume of saline delivered will be equivalent to the volume of saline that the subject receives during the BNP infusion visit.
normal saline (placebo): Subjects will receive an IV infusion of normal saline for 240 minutes. The volume of saline delivered will be equivalent to the volume of saline that the subject receives during the BNP infusion visit.
recombinant human BNP (1-32): Subjects will receive an IV infusion of recombinant human BNP1-32 (6 mcg BNP/ml saline) for 240 minutes.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Local skin reaction
|
40.0%
2/5 • Number of events 3 • Approximately 1 year
|
20.0%
1/5 • Number of events 1 • Approximately 1 year
|
|
Cardiac disorders
Vasovagal response
|
0.00%
0/5 • Approximately 1 year
|
20.0%
1/5 • Number of events 2 • Approximately 1 year
|
|
Musculoskeletal and connective tissue disorders
Finger Fracture prior to intervention (unrelated to study)
|
20.0%
1/5 • Number of events 1 • Approximately 1 year
|
0.00%
0/5 • Approximately 1 year
|
|
Vascular disorders
Headache
|
20.0%
1/5 • Number of events 1 • Approximately 1 year
|
0.00%
0/5 • Approximately 1 year
|
|
Gastrointestinal disorders
Nausea
|
20.0%
1/5 • Number of events 1 • Approximately 1 year
|
0.00%
0/5 • Approximately 1 year
|
Additional Information
Alp Ikizler, Catherine McLaughlin Hakim Chair in Vascular Biology, Professor of Medicine
Vanderbilt University Medical Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place