Pharmacogenetics of Ace Inhibitor-Associated Angioedema

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Nancy J. Brown, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01413542
First received: August 8, 2011
Last updated: October 5, 2015
Last verified: October 2015
Results First Received: November 7, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Hypertension
Diabetes Type 2
Interventions: Drug: Sitagliptin (DPP4 inhibitor)
Drug: Substance P,
Drug: bradykinin
Drug: enalaprilat (ACE inhibitor)
Drug: Glucagon-like peptide 1
Drug: brain natriuretic peptide

  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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
44 participants were enrolled in this study (23 in Group 1 and 21 in Group 2) and completed screening procedures. Twelve of 23 participants met inclusion and exclusion criteria and completed all study-related procedures in Group 1. Seventeen of 21 participants met inclusion/exclusion criteria and completed all study-related procedures in Group 2.

Reporting Groups
  Description
Placebo Then Sitagliptin (DPP4 Inhibibition)=Group 1 Participants first received Placebo then Sitagliptin 200 mg by mouth one time on each of two study days. Two weeks separated each study day. Each study day examined the effect of vehicle and enalaprilat on the forearm blood flow and tPA responses to bradykinin and substance P.
Sitagliptin (DPP4 Inhibition) Then Placebo=Group 1 Participants first received Sitagliptin 200 mg then Placebo by mouth one time on each of two study days. Two weeks separated each study day. Each study day examined the effect of vehicle and enalaprilat on the forearm blood flow and tPA responses to bradykinin and substance P.
Placebo Then Sitagliptin (DPP4 Inhibition)=Group 2 Participants first received Placebo then Sitagliptin 200 mg by mouth one time on each of two study days. Two weeks separated each study day. Each study day examined the forearm blood flow and tPA responses to brain natriuretic peptide (BNP) and glucagon-like receptor 1 (GLP-1).
Sitagliptin (DPP4 Inhibition) Then Placebo = Group 2 Participants first received Sitagliptin 200 mg then Placebo by mouth one time on each of two study days. Two weeks separated each study day. Each study day examined the forearm blood flow and tPA responses to brain natriuretic peptide (BNP) and glucagon-like receptor 1 (GLP-1).

Participant Flow:   Overall Study
    Placebo Then Sitagliptin (DPP4 Inhibibition)=Group 1     Sitagliptin (DPP4 Inhibition) Then Placebo=Group 1     Placebo Then Sitagliptin (DPP4 Inhibition)=Group 2     Sitagliptin (DPP4 Inhibition) Then Placebo = Group 2  
STARTED     6     6     9     8  
COMPLETED     5     6     6     7  
NOT COMPLETED     1     0     3     1  
Physician Decision                 1                 0                 3                 0  
Adverse Event                 0                 0                 0                 1  



  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.
This population represents the 29 participants (12 in Group 1; 17 in Group 2) who passed screening and completed at least one study arm. 1 subject did not complete the 2nd arm in Group 1. 4 subjects did not complete the second arm in Group 2. Results and baseline characteristics are presented inclusive of these patients.

Reporting Groups
  Description
Group 1 Participants were randomized to sitagliptin 200 mg vs. placebo on each of two study days. On each study day, the effects of vehicle and enalaprilat on forearm blood flow and tPA responses to bradykinin and substance P were studied.
Group 2 Participants were randomized to sitagliptin 200 mg vs. placebo on each of two study days. On each study day, the effect of brain natriuretic peptide and glucagon like receptor-1 (GLP-1) on forearm blood flow and tPA release was studied.
Total Total of all reporting groups

Baseline Measures
    Group 1     Group 2     Total  
Number of Participants  
[units: participants]
  12     17     29  
Age  
[units: years]
Mean (Standard Deviation)
  38.1  (12.0)     35.4  (10.0)     36.5  (10.7)  
Gender  
[units: participants]
     
Female     7     8     15  
Male     5     9     14  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     3     5     8  
White     9     12     21  
More than one race     0     0     0  
Unknown or Not Reported     0     0     0  
Region of Enrollment  
[units: participants]
     
United States     12     17     29  



  Outcome Measures
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1.  Primary:   The Effect of Enalaprilat (ACE Inhibition), Sitagliptin (DPP4 Inhibition), or the Combination on the Vasodilator Response (Forearm Blood Flow) to Substance P (SP) and Bradykinin (Group 1) or Glucagon Like Peptide-1 and Brain Naturetic Peptide (Group 2).   [ Time Frame: 60 minutes post-placebo or sitagliptin (DPP4 inhibition) and over last 2 minutes of each 5 min infusion per peptide dose (30 min washout between peptides); sequence repeated with enalaprilat (ACE inhibition) or vehicle ]

2.  Secondary:   Assess Tissue Type Plasminogen Activator (tPA) Release   [ Time Frame: Blood for analysis of tPA release was obtained 60 minutes after sitagliptin (DPP4 inhibition) vs. placebo and after each assessment of FBF (see primary outcome measure) ]

3.  Secondary:   Assess Effect of ACE and/or DPP4 Inhibition on Heart Rate Response to Substance P (SP)   [ Time Frame: Heart rate was measured every 5 minutes throughout the study day (and thus during each dose of peptide infusion) ]

4.  Secondary:   Effect of Treatment (ACE or DPP4 Inhibition, or Combined) on Norepinephrine (NE) Release (Arterial Venous Gradient) in Response to Substance P (SP)   [ Time Frame: Blood for analysis of norepinephrine (NE) release was obtained 60 minutes after sitagliptin (DPP4 inhibition) vs. placebo and after each assessment of FBF (see primary outcome measure) ]

5.  Secondary:   Effect of Treatment (DPP4 Inhibition vs. Placebo) on Venous GLP-1 Levels in Response to Arterial GLP-1 Infusion   [ Time Frame: Blood for analysis of GLP-1 levels was obtained one hour after sitagliptin (DPP4 inhibition) vs. placebo administration and after each dose of GLP-1 ]


  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
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  More Information
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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.


Results Point of Contact:  
Name/Title: Dr. Nancy J. Brown
Organization: Department of Medicine Vanderbilt University Medical Center
phone: 615-343-8701
e-mail: nancy.j.brown@vanderbilt.edu


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Nancy J. Brown, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01413542     History of Changes
Obsolete Identifiers: NCT00139503
Other Study ID Numbers: HL079184
Study First Received: August 8, 2011
Results First Received: November 7, 2014
Last Updated: October 5, 2015
Health Authority: United States: Food and Drug Administration