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Natriuretic Peptide System as Therapy in Human Preclinical Left Ventricle Dysfunction (PPG1)

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Horng Chen, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00387621
First received: October 12, 2006
Last updated: April 18, 2012
Last verified: April 2012
Results First Received: October 26, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacodynamics Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Basic Science
Condition: Congestive Heart Failure
Interventions: Drug: Nesiritide
Drug: Placebo
Drug: Saline

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study took place between February 2006 and August 2009. All subjects were consented and were seen at the Mayo Clinic in Rochester, MN.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
63 participants were enrolled in the study, but 5 participants were excluded because they did not meet inclusion criteria. Participants included normal controls, Preclinical Systolic Dysfunction, and Preclinical Diastolic Dysfunction subjects, who were randomized into Placebo First, then Nesiritide (Arm A) and Nesiritide First, then Placebo (Arm B)

Reporting Groups
  Description
Placebo First, Then Nesiritide (Arm A) In the first intervention period the subjects received subcutaneous placebo given in the abdomen. After a lead in period of 15 minutes, the acute saline load was administered. There was a 2 week washout period. In the second intervention period, the subjects received subcutaneous nesiritide given in the abdomen. After a lead in period of 15 minutes, the acute saline load was administered.
Nesiritide First, Then Placebo (Arm B) In the first intervention period the subjects received subcutaneous nesiritide given in the abdomen. After a lead in period of 15 minutes, the acute saline load was administered. There was a 2 week washout period. In the second intervention period, the subjects received subcutaneous placebo given in the abdomen. After a lead in period of 15 minutes, the acute saline load was administered.

Participant Flow for 3 periods

Period 1:   First Intervention
    Placebo First, Then Nesiritide (Arm A)     Nesiritide First, Then Placebo (Arm B)  
STARTED     29     29  
COMPLETED     29     29  
NOT COMPLETED     0     0  

Period 2:   Washout Period of 2 Weeks
    Placebo First, Then Nesiritide (Arm A)     Nesiritide First, Then Placebo (Arm B)  
STARTED     29     29  
COMPLETED     29     29  
NOT COMPLETED     0     0  

Period 3:   Second Intervention
    Placebo First, Then Nesiritide (Arm A)     Nesiritide First, Then Placebo (Arm B)  
STARTED     29     29  
COMPLETED     29     29  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Control Group (Normals) Healthy volunteers without heart disease
Preclinical Systolic Dysfunction Group (PSD) Participants with ejection fraction <40% and no heart failure symptoms
Preclinical Diastolic Dysfunction Group (PDD) Participants with an ejection fraction of > 50% and no heart failure symptoms
Total Total of all reporting groups

Baseline Measures
    Control Group (Normals)     Preclinical Systolic Dysfunction Group (PSD)     Preclinical Diastolic Dysfunction Group (PDD)     Total  
Number of Participants  
[units: participants]
  20     20     18     58  
Age  
[units: years]
Mean ± Standard Deviation
  37  ± 11     65  ± 12     72  ± 7     57.5  ± 18.4  
Gender  
[units: participants]
       
Female     17     2     9     28  
Male     3     18     9     30  
Region of Enrollment  
[units: participants]
       
United States     20     20     18     58  
Creatinine  
[units: mg/dL]
Mean ± Standard Deviation
  0.9  ± 0.1     1.1  ± 0.2     1.1  ± 0.3     1.0  ± 0.2  
Blood Urea Nitrogen  
[units: mg/dL]
Mean ± Standard Deviation
  11  ± 5     21  ± 10     23  ± 6     18.2  ± 8.6  
Body Mass Index [1]
[units: kg/m^2]
Mean ± Standard Deviation
  25  ± 4     31  ± 5     30  ± 5     28.5  ± 5.1  
[1]

Body mass index (BMI) is a measure of body fat based on height and weight that applies to adult men and women.

BMI Categories:

Underweight = <18.5 Normal weight = 18.5–24.9 Overweight = 25–29.9 Obesity = BMI of 30 or greater




  Outcome Measures
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1.  Primary:   Change in Natriuresis (Urinary Sodium Excretion) in Control Subjects at 60 Minutes After Volume Expansion Compared to Baseline in Response to Placebo Treatment   [ Time Frame: baseline and 60 minutes ]

2.  Primary:   Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV)   [ Time Frame: Baseline, 30 min, 60 min ]

3.  Primary:   Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV)   [ Time Frame: Baseline, 30 min, 60 min ]

4.  Primary:   Nesiritide Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UNaV)   [ Time Frame: Baseline, 30 min, 60 min ]

5.  Primary:   Nesiritide Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV)   [ Time Frame: Baseline, 30 min, 60 min ]

6.  Secondary:   Change in Urinary Cyclic Guanosine Monophosphate (cGMP) in Control Subjects at 60 Minutes After Volume Expansion Compared to Baseline in Response to Placebo Treatment   [ Time Frame: baseline and 60 minutes ]

7.  Secondary:   Change in Natriuresis (Urinary Sodium Excretion) at 30 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment   [ Time Frame: 30 minutes ]

8.  Secondary:   Change in Natriuresis (Urinary Sodium Excretion) at 60 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment   [ Time Frame: 60 minutes ]

9.  Secondary:   Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 30 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment   [ Time Frame: 30 minutes ]

10.  Secondary:   Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 60 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment   [ Time Frame: 60 minutes ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
  • Different baseline characteristics of the three groups of subjects
  • Did not define a mechanism for the impaired renal cGMP activation
  • Future studies needed to determine effects of chronic nesiritide therapy in preclinical HF.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Dr Horng Chen
Organization: Mayo Clinic
phone: 507-284-4343
e-mail: chen.horng@mayo.edu


Publications:

Responsible Party: Horng Chen, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00387621     History of Changes
Obsolete Identifiers: NCT00818974
Other Study ID Numbers: 05-004027, P01HL076611, R01HL084155, UL1RR024150
Study First Received: October 12, 2006
Results First Received: October 26, 2011
Last Updated: April 18, 2012
Health Authority: United States: Food and Drug Administration