Trial Outcomes & Findings for Aldosterone and the Metabolic Syndrome (NCT NCT01103245)
NCT ID: NCT01103245
Last Updated: 2018-11-05
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
69 participants
Primary outcome timeframe
at the end of each 1 month study period ( 3 times in total)
Results posted on
2018-11-05
Participant Flow
31 of the consented participants did not meet inclusion criteria and did not participate in the study
Participant milestones
| Measure |
HCTZ Plus ALI 150 Then ALI 300
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)
|
HCTZ Plus ALI 150 Then 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 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)
|
HCTZ Plus SPL 25 Then SPL 50
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)
|
HCTZ Plus SPL 25 Then ALI 150 and SPL 25
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 Study
STARTED
|
13
|
7
|
12
|
6
|
|
Overall Study
COMPLETED
|
10
|
5
|
8
|
6
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
4
|
0
|
Reasons for withdrawal
| Measure |
HCTZ Plus ALI 150 Then ALI 300
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)
|
HCTZ Plus ALI 150 Then 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 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)
|
HCTZ Plus SPL 25 Then SPL 50
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)
|
HCTZ Plus SPL 25 Then ALI 150 and SPL 25
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 Study
Withdrawal by Subject
|
1
|
0
|
3
|
0
|
|
Overall Study
Inadequate IV access
|
1
|
0
|
0
|
0
|
|
Overall Study
Adverse Event
|
0
|
2
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Aldosterone and the Metabolic Syndrome
Baseline characteristics by cohort
| Measure |
HCTZ Plus ALI 150 Then ALI 300
n=13 Participants
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)
|
HCTZ Plus ALI 150 Then ALI 150 and SPL 25
n=7 Participants
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)
|
HCTZ Plus SPL 25 Then SPL 50
n=12 Participants
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)
|
HCTZ Plus SPL 25 Then ALI 150 and SPL 25
n=6 Participants
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
n=38 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
13 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
38 Participants
n=36 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Age, Continuous
|
46.8 years
STANDARD_DEVIATION 11.8 • n=93 Participants
|
46.8 years
STANDARD_DEVIATION 8.4 • n=4 Participants
|
44.0 years
STANDARD_DEVIATION 11.6 • n=27 Participants
|
42.8 years
STANDARD_DEVIATION 13.8 • n=483 Participants
|
45.3 years
STANDARD_DEVIATION 11.2 • n=36 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
19 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
19 Participants
n=36 Participants
|
|
Region of Enrollment
United States
|
13 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
38 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: at the end of each 1 month study period ( 3 times in total)Population: 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.
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.
Outcome measures
| Measure |
HCTZ Plus ALI 150 Then ALI 300
n=12 Participants
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)
|
HCTZ Plus ALI 150 Then ALI 150 and SPL 25
n=7 Participants
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)
|
HCTZ Plus SPL 25 Then SPL 50
n=11 Participants
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)
|
HCTZ Plus SPL 25 Then ALI 150 and SPL 25
n=6 Participants
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)
|
|---|---|---|---|---|
|
Plasma Insulin
Baseline, HCTZ Only
|
75.4 uU/ml
Standard Deviation 82.7
|
50.1 uU/ml
Standard Deviation 40.1
|
43.5 uU/ml
Standard Deviation 23.9
|
114.0 uU/ml
Standard Deviation 93.1
|
|
Plasma Insulin
HCTZ + ALI 150
|
54.8 uU/ml
Standard Deviation 50.2
|
43.3 uU/ml
Standard Deviation 33.0
|
—
|
—
|
|
Plasma Insulin
HCTZ + ALI 300
|
75.7 uU/ml
Standard Deviation 76.6
|
—
|
—
|
—
|
|
Plasma Insulin
HCTZ + ALI 150 and SPL 25
|
—
|
69.1 uU/ml
Standard Deviation 37.3
|
—
|
99.9 uU/ml
Standard Deviation 32.0
|
|
Plasma Insulin
HCTZ + SPL 25
|
—
|
—
|
53.4 uU/ml
Standard Deviation 36.6
|
113.2 uU/ml
Standard Deviation 99.7
|
|
Plasma Insulin
HCTZ + SPL 50
|
—
|
—
|
44.3 uU/ml
Standard Deviation 18.3
|
—
|
PRIMARY outcome
Timeframe: at the end of each 1 month study period ( 3 times in total)Population: 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
Fasting plasma glucose, measured during hyperglycemic clamp
Outcome measures
| Measure |
HCTZ Plus ALI 150 Then ALI 300
n=12 Participants
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)
|
HCTZ Plus ALI 150 Then ALI 150 and SPL 25
n=7 Participants
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)
|
HCTZ Plus SPL 25 Then SPL 50
n=11 Participants
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)
|
HCTZ Plus SPL 25 Then ALI 150 and SPL 25
n=6 Participants
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)
|
|---|---|---|---|---|
|
Plasma Glucose
HCTZ + ALI 150
|
119.7 mg/dl
Standard Deviation 39.7
|
105.7 mg/dl
Standard Deviation 20.4
|
—
|
—
|
|
Plasma Glucose
Baseline, HCTZ Only
|
108.6 mg/dl
Standard Deviation 24.1
|
106.1 mg/dl
Standard Deviation 18.1
|
96.4 mg/dl
Standard Deviation 10.1
|
102.2 mg/dl
Standard Deviation 18.4
|
|
Plasma Glucose
HCTZ + ALI 300
|
111.4 mg/dl
Standard Deviation 25.3
|
—
|
—
|
—
|
|
Plasma Glucose
HCTZ + ALI 150 and SPL 25
|
—
|
102.1 mg/dl
Standard Deviation 10.9
|
—
|
107.2 mg/dl
Standard Deviation 17.3
|
|
Plasma Glucose
HCTZ + SPL 25
|
—
|
—
|
104.8 mg/dl
Standard Deviation 10.7
|
101.7 mg/dl
Standard Deviation 11.5
|
|
Plasma Glucose
HCTZ + SPL 50
|
—
|
—
|
105.9 mg/dl
Standard Deviation 10.7
|
—
|
Adverse Events
HCTZ Plus ALI 150 Then ALI 300
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
HCTZ Plus ALI 150 Then ALI 150 and SPL 25
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
HCTZ Plus SPL 25 Then SPL 50
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
HCTZ Plus SPL 25 Then ALI 150 and SPL 25
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
HCTZ Plus ALI 150 Then ALI 300
n=13 participants at risk
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)
|
HCTZ Plus ALI 150 Then ALI 150 and SPL 25
n=7 participants at risk
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)
|
HCTZ Plus SPL 25 Then SPL 50
n=12 participants at risk
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)
|
HCTZ Plus SPL 25 Then ALI 150 and SPL 25
n=6 participants at risk
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)
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
15.4%
2/13 • Number of events 2
|
14.3%
1/7 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Blood and lymphatic system disorders
IV irritation
|
7.7%
1/13 • Number of events 1
|
0.00%
0/7
|
25.0%
3/12 • Number of events 3
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Cramp
|
23.1%
3/13 • Number of events 3
|
42.9%
3/7 • Number of events 3
|
8.3%
1/12 • Number of events 1
|
0.00%
0/6
|
|
Cardiac disorders
Dizziness or Lightheadedness
|
0.00%
0/13
|
14.3%
1/7 • Number of events 1
|
0.00%
0/12
|
0.00%
0/6
|
|
General disorders
Fatigue
|
0.00%
0/13
|
28.6%
2/7 • Number of events 2
|
0.00%
0/12
|
0.00%
0/6
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place