ClinicalTrials.gov
ClinicalTrials.gov Menu

Aldosterone and the Metabolic Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01103245
Recruitment Status : Completed
First Posted : April 14, 2010
Results First Posted : November 5, 2018
Last Update Posted : November 5, 2018
Sponsor:
Information provided by (Responsible Party):
James Matt Luther, Vanderbilt University Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Interventions Drug: Hydrochlorothiazide (HCTZ)
Drug: Aliskiren 150 mg (ALI 150)
Drug: Spironolactone (SPL 25)
Drug: Aliskiren 300 mg (ALI 300)
Drug: Spironolactone 50 mg (SPL 50)
Enrollment 69
Recruitment Details  
Pre-assignment Details 31 of the consented participants did not meet inclusion criteria and did not participate in the study
Arm/Group Title HCTZ Plus ALI 150 Then ALI 300 HCTZ Plus ALI 150 Then ALI 150 and SPL 25 HCTZ Plus SPL 25 Then SPL 50 HCTZ Plus SPL 25 Then ALI 150 and SPL 25
Hide Arm/Group Description Baseline: HCTZ 12.5mg daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Aliskiren 150 mg daily for 1 month (HCTZ + ALI 150), then Period 2: HCTZ 12.5mg daily plus Aliskiren 300mg for 1 month (HCTZ + ALI 300) Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Aliskiren 150 mg daily for 1 month (HCTZ + ALI 150), then Period 2: HCTZ 12.5mg daily plus Aliskiren 150 mg daily and Spironolactone 25 mg daily for one month (HCTZ + ALI 150 and SPL 25) Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Spironolactone 25 mg daily for 1 month (HCTZ + SPL 25), then Period 2: HCTZ 12.5mg daily plus Spironolactone 50 mg daily for one month (HCTZ + SPL 50) Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only) Period 1: HCTZ 12.5mg daily plus Spironolactone 25 mg daily for 1 month (HCTZ + SPL 25) Period 2: HCTZ 12.5mg daily plus Aliskiren 150 mg daily and Spironolactone 25 mg daily for one month (HCTZ + ALI 150 and SPL 25)
Period Title: Overall Study
Started 13 7 12 6
Completed 10 5 8 6
Not Completed 3 2 4 0
Reason Not Completed
Withdrawal by Subject             1             0             3             0
Inadequate IV access             1             0             0             0
Adverse Event             0             2             1             0
Physician Decision             1             0             0             0
Arm/Group Title HCTZ Plus ALI 150 Then ALI 300 HCTZ Plus ALI 150 Then ALI 150 and SPL 25 HCTZ Plus SPL 25 Then SPL 50 HCTZ Plus SPL 25 Then ALI 150 and SPL 25 Total
Hide Arm/Group Description Baseline: HCTZ 12.5mg daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Aliskiren 150 mg daily for 1 month (HCTZ + ALI 150), then Period 2: HCTZ 12.5mg daily plus Aliskiren 300mg for 1 month (HCTZ + ALI 300) Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Aliskiren 150 mg daily for 1 month (HCTZ + ALI 150), then Period 2: HCTZ 12.5mg daily plus Aliskiren 150 mg daily and Spironolactone 25 mg daily for one month (HCTZ + ALI 150 and SPL 25) Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Spironolactone 25 mg daily for 1 month (HCTZ + SPL 25), then Period 2: HCTZ 12.5mg daily plus Spironolactone 50 mg daily for one month (HCTZ + SPL 50) Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only) Period 1: HCTZ 12.5mg daily plus Spironolactone 25 mg daily for 1 month (HCTZ + SPL 25) Period 2: HCTZ 12.5mg daily plus Aliskiren 150 mg daily and Spironolactone 25 mg daily for one month (HCTZ + ALI 150 and SPL 25) Total of all reporting groups
Overall Number of Baseline Participants 13 7 12 6 38
Hide Baseline Analysis Population Description
subjects who received drug but dropped out before study outcome measures could be obtained were excluded from final analysis
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 7 participants 12 participants 6 participants 38 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
13
 100.0%
7
 100.0%
12
 100.0%
6
 100.0%
38
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 7 participants 12 participants 6 participants 38 participants
46.8  (11.8) 46.8  (8.4) 44.0  (11.6) 42.8  (13.8) 45.3  (11.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 7 participants 12 participants 6 participants 38 participants
Female
9
  69.2%
3
  42.9%
6
  50.0%
1
  16.7%
19
  50.0%
Male
4
  30.8%
4
  57.1%
6
  50.0%
5
  83.3%
19
  50.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 13 participants 7 participants 12 participants 6 participants 38 participants
13
 100.0%
7
 100.0%
12
 100.0%
6
 100.0%
38
 100.0%
1.Primary Outcome
Title Plasma Insulin
Hide Description A Hyperglycemic clamp was performed once during each study period to assess glucose stimulated insulin secretion. Glucose is infused intravenously to maintain blood glucose near 200 mg/dL to stimulate insulin secretion. During this time plasma insulin levels were measured and the insulin response is reported as the incremental increase over the first 10 minutes of glucose administration.
Time Frame at the end of each 1 month study period ( 3 times in total)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
2 participants were excluded from the final analysis because they did not complete any of the Hyperglycemic clamps:1 from the HCTZ plus ALI150 then ALI 300 group and 1 participant from the HCTZ plus SPL 25 then ALI 150 and SPL 25 group.
Arm/Group Title HCTZ Plus ALI 150 Then ALI 300 HCTZ Plus ALI 150 Then ALI 150 and SPL 25 HCTZ Plus SPL 25 Then SPL 50 HCTZ Plus SPL 25 Then ALI 150 and SPL 25
Hide Arm/Group Description:
Baseline: HCTZ 12.5mg daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Aliskiren 150 mg daily for 1 month (HCTZ + ALI 150), then Period 2: HCTZ 12.5mg daily plus Aliskiren 300mg for 1 month (HCTZ + ALI 300)
Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Aliskiren 150 mg daily for 1 month (HCTZ + ALI 150), then Period 2: HCTZ 12.5mg daily plus Aliskiren 150 mg daily and Spironolactone 25 mg daily for one month (HCTZ + ALI 150 and SPL 25)
Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Spironolactone 25 mg daily for 1 month (HCTZ + SPL 25), then Period 2: HCTZ 12.5mg daily plus Spironolactone 50 mg daily for one month (HCTZ + SPL 50)
Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only) Period 1: HCTZ 12.5mg daily plus Spironolactone 25 mg daily for 1 month (HCTZ + SPL 25) Period 2: HCTZ 12.5mg daily plus Aliskiren 150 mg daily and Spironolactone 25 mg daily for one month (HCTZ + ALI 150 and SPL 25)
Overall Number of Participants Analyzed 12 7 11 6
Mean (Standard Deviation)
Unit of Measure: uU/ml
Baseline, HCTZ Only Number Analyzed 12 participants 7 participants 11 participants 6 participants
75.4  (82.7) 50.1  (40.1) 43.5  (23.9) 114.0  (93.1)
HCTZ + ALI 150 Number Analyzed 12 participants 6 participants 0 participants 0 participants
54.8  (50.2) 43.3  (33.0)
HCTZ + ALI 300 Number Analyzed 10 participants 0 participants 0 participants 0 participants
75.7  (76.6)
HCTZ + ALI 150 and SPL 25 Number Analyzed 0 participants 5 participants 0 participants 6 participants
69.1  (37.3) 99.9  (32.0)
HCTZ + SPL 25 Number Analyzed 0 participants 0 participants 10 participants 6 participants
53.4  (36.6) 113.2  (99.7)
HCTZ + SPL 50 Number Analyzed 0 participants 0 participants 8 participants 0 participants
44.3  (18.3)
2.Primary Outcome
Title Plasma Glucose
Hide Description Fasting plasma glucose, measured during hyperglycemic clamp
Time Frame at the end of each 1 month study period ( 3 times in total)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
2 participants were excluded from the final analysis because they did not complete any of the Hyperglycemic clamps:1 from the HCTZ plus ALI150 then ALI 300 group and 1 participant from the HCTZ plus SPL 25 then ALI 150 and SPL 25 group
Arm/Group Title HCTZ Plus ALI 150 Then ALI 300 HCTZ Plus ALI 150 Then ALI 150 and SPL 25 HCTZ Plus SPL 25 Then SPL 50 HCTZ Plus SPL 25 Then ALI 150 and SPL 25
Hide Arm/Group Description:
Baseline: HCTZ 12.5mg daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Aliskiren 150 mg daily for 1 month (HCTZ + ALI 150), then Period 2: HCTZ 12.5mg daily plus Aliskiren 300mg for 1 month (HCTZ + ALI 300)
Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Aliskiren 150 mg daily for 1 month (HCTZ + ALI 150), then Period 2: HCTZ 12.5mg daily plus Aliskiren 150 mg daily and Spironolactone 25 mg daily for one month (HCTZ + ALI 150 and SPL 25)
Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Spironolactone 25 mg daily for 1 month (HCTZ + SPL 25), then Period 2: HCTZ 12.5mg daily plus Spironolactone 50 mg daily for one month (HCTZ + SPL 50)
Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only) Period 1: HCTZ 12.5mg daily plus Spironolactone 25 mg daily for 1 month (HCTZ + SPL 25) Period 2: HCTZ 12.5mg daily plus Aliskiren 150 mg daily and Spironolactone 25 mg daily for one month (HCTZ + ALI 150 and SPL 25)
Overall Number of Participants Analyzed 12 7 11 6
Mean (Standard Deviation)
Unit of Measure: mg/dl
Baseline, HCTZ Only Number Analyzed 12 participants 7 participants 11 participants 6 participants
108.6  (24.1) 106.1  (18.1) 96.4  (10.1) 102.2  (18.4)
HCTZ + ALI 150 Number Analyzed 12 participants 6 participants 0 participants 0 participants
119.7  (39.7) 105.7  (20.4)
HCTZ + ALI 300 Number Analyzed 10 participants 0 participants 0 participants 0 participants
111.4  (25.3)
HCTZ + ALI 150 and SPL 25 Number Analyzed 0 participants 5 participants 0 participants 6 participants
102.1  (10.9) 107.2  (17.3)
HCTZ + SPL 25 Number Analyzed 0 participants 0 participants 10 participants 6 participants
104.8  (10.7) 101.7  (11.5)
HCTZ + SPL 50 Number Analyzed 0 participants 0 participants 8 participants 0 participants
105.9  (10.7)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title HCTZ Plus ALI 150 Then ALI 300 HCTZ Plus ALI 150 Then ALI 150 and SPL 25 HCTZ Plus SPL 25 Then SPL 50 HCTZ Plus SPL 25 Then ALI 150 and SPL 25
Hide Arm/Group Description Baseline: HCTZ 12.5mg daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Aliskiren 150 mg daily for 1 month (HCTZ + ALI 150), then Period 2: HCTZ 12.5mg daily plus Aliskiren 300mg for 1 month (HCTZ + ALI 300) Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Aliskiren 150 mg daily for 1 month (HCTZ + ALI 150), then Period 2: HCTZ 12.5mg daily plus Aliskiren 150 mg daily and Spironolactone 25 mg daily for one month (HCTZ + ALI 150 and SPL 25) Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only), then Period 1: HCTZ 12.5mg daily plus Spironolactone 25 mg daily for 1 month (HCTZ + SPL 25), then Period 2: HCTZ 12.5mg daily plus Spironolactone 50 mg daily for one month (HCTZ + SPL 50) Baseline: HCTZ 12.5mg HCTZ daily for 1 month (Baseline, HCTZ only) Period 1: HCTZ 12.5mg daily plus Spironolactone 25 mg daily for 1 month (HCTZ + SPL 25) Period 2: HCTZ 12.5mg daily plus Aliskiren 150 mg daily and Spironolactone 25 mg daily for one month (HCTZ + ALI 150 and SPL 25)
All-Cause Mortality
HCTZ Plus ALI 150 Then ALI 300 HCTZ Plus ALI 150 Then ALI 150 and SPL 25 HCTZ Plus SPL 25 Then SPL 50 HCTZ Plus SPL 25 Then ALI 150 and SPL 25
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/13 (0.00%)      0/7 (0.00%)      0/12 (0.00%)      0/6 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
HCTZ Plus ALI 150 Then ALI 300 HCTZ Plus ALI 150 Then ALI 150 and SPL 25 HCTZ Plus SPL 25 Then SPL 50 HCTZ Plus SPL 25 Then ALI 150 and SPL 25
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/13 (0.00%)      0/7 (0.00%)      0/12 (0.00%)      0/6 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
HCTZ Plus ALI 150 Then ALI 300 HCTZ Plus ALI 150 Then ALI 150 and SPL 25 HCTZ Plus SPL 25 Then SPL 50 HCTZ Plus SPL 25 Then ALI 150 and SPL 25
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/13 (46.15%)      7/7 (100.00%)      5/12 (41.67%)      1/6 (16.67%)    
Blood and lymphatic system disorders         
IV irritation  [1]  1/13 (7.69%)  1 0/7 (0.00%)  0 3/12 (25.00%)  3 0/6 (0.00%)  0
Cardiac disorders         
Dizziness or Lightheadedness * [2]  0/13 (0.00%)  0 1/7 (14.29%)  1 0/12 (0.00%)  0 0/6 (0.00%)  0
General disorders         
Fatigue * [3]  0/13 (0.00%)  0 2/7 (28.57%)  2 0/12 (0.00%)  0 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Cramp * [4]  3/13 (23.08%)  3 3/7 (42.86%)  3 1/12 (8.33%)  1 0/6 (0.00%)  0
Nervous system disorders         
Headache * [5]  2/13 (15.38%)  2 1/7 (14.29%)  1 1/12 (8.33%)  1 1/6 (16.67%)  1
Indicates events were collected by systematic assessment
[1]
Irritation at IV site
*
Indicates events were collected by non-systematic assessment
[2]
Dizziness or lightheadedness, without fall or syncope
[3]
Generalized fatigue
[4]
muscle cramping
[5]
Headache, transient
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: James M. Luther
Organization: Vanderbilt University Medical Center
Phone: (615) 936-3420
Responsible Party: James Matt Luther, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT01103245     History of Changes
Other Study ID Numbers: 091072
09CRP2261428 ( Other Grant/Funding Number: American Heart Association )
First Submitted: April 12, 2010
First Posted: April 14, 2010
Results First Submitted: April 19, 2017
Results First Posted: November 5, 2018
Last Update Posted: November 5, 2018