Trial Outcomes & Findings for Leptin Infusion and Endothelial Vasomotor Response (NCT NCT04374500)
NCT ID: NCT04374500
Last Updated: 2023-05-09
Results Overview
The primary outcome in all protocols were local blood-flow in the forearm (FBF). This was measured by venous occlusion plethysmography using mercury-in-silastic strain gauges and the unit is mL/100mL of tissue/min. In protocol 1, the FBF response to increasing levels of leptin was evaluated, In protocol 2, the FBF response to vasodilators on top of leptin or saline infusion was evaluated, and in protocol 3, FBF was measured after infusion of vasodilators and no leptin was given.
COMPLETED
EARLY_PHASE1
103 participants
18 minutes in protocol 1, 3 hours in protocol 2, non-applicable (NA) in protocol 3
2023-05-09
Participant Flow
Twenty (20) healthy non-smoking male volunteers not taking any regular medication were recruited in Umeå, Sweden, ten (10) participated in protocol 1 and ten (10) in protocol 2. Eighty-three (83) men and women with established coronary artery disease were recruited from the cardiology outpatient clinic at the Royal Infirmary, Edinburgh, Scotland.
Protocol 1 and 2 were performed in Umeå, Sweden. The two protocols were separated in time (approximately 6 months). The total number of participants were 10+10 men, with altogether 30 examinations (protocol 1 - examined once and protocol 2 - examined twice). Protocol 3 was performed in UK, and 83 participants were examined once. Thus 103 participants with 113 examinations.
Participant milestones
| Measure |
Leptin Infusion in Healthy Men
This applies to protocol 1 when 10 healthy men got infusion of leptin locally and forearm blood flow was measured with the other arm as the control.
|
Leptin or Saline Infusion Plus Vasodilators in Healthy Men
This applies to protocol 2 when 10 healthy men got either a background infusion of leptin or saline when measuring vasoresponse to four vasodilatators. Each participant had two examinations with either leptin or saline and the order was randomised.
|
Vasodilators in CAD Patients
This applies to protocol 3 when blood flow was measured in the forearm after infusion of 3 vasodilators, and leptin was not infused
|
|---|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
83
|
|
Overall Study
COMPLETED
|
10
|
10
|
83
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Mean (SD) are given for age at baseline examination for 20 healthy males in protocol 1 and 2, and for 83 men and women with CAD in protocol 3.
Baseline characteristics by cohort
| Measure |
Healthy Males and CAD Patients
n=103 Participants
Arm 1: Healthy males (n=10). Leptin was infused intra-arterially (IA) at ascending doses of 80, 800 and 8,000 ng/min. Bilateral forearm blood flow (FBF), heart rate, blood pressure, leptin, tissue plasminogen activator (tPA) antigen were determined.
Arm 2: Healthy males (n=10). Leptin (800 ng/min) or saline was given IA with at least 2 weeks between visits. Vasodilators were infused concomitantly with IA leptin/saline infusions; bradykinin at 100, 300 and 1,000 pmol/min, acetylcholine (AcCh) at 5, 10 and 20 µg/min, sodium nitroprusside (SNP) at 2, 4 and 8 µg/min and verapamil at 10, 30, 100 µg/min, for 6 minutes at each concentration. Bilateral FBF, heart rate, blood pressure, leptin, tPA antigen were determined.
Arm 3: CAD patients (n=83). IA infusions of substance P at 2, 4 and 8 pmol/min, AcCh at 5, 10 and 20 µg/min, and SNP at 2, 4 and 8 µg/min were given. Bilateral FBF, heart rate, blood pressure, leptin, tPA antigen were determined.
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|---|---|
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Age, Continuous
Healthy males
|
26.4 Years
STANDARD_DEVIATION 5.8 • n=20 Participants • Mean (SD) are given for age at baseline examination for 20 healthy males in protocol 1 and 2, and for 83 men and women with CAD in protocol 3.
|
|
Age, Continuous
Coronary artery disease (CAD) patients
|
60 Years
STANDARD_DEVIATION 6 • n=83 Participants • Mean (SD) are given for age at baseline examination for 20 healthy males in protocol 1 and 2, and for 83 men and women with CAD in protocol 3.
|
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Sex: Female, Male
Female
|
17 Participants
n=103 Participants
|
|
Sex: Female, Male
Male
|
86 Participants
n=103 Participants
|
|
Region of Enrollment
United Kingdom
|
83 Participants
n=83 Participants • Protocol 1 and 2 was performed in Sweden, 10 participants and 30 examinations.
|
|
Region of Enrollment
Sweden
|
20 Participants
n=20 Participants • Protocol 1 and 2 was performed in Sweden, 10 participants and 30 examinations.
|
|
tPA antigen
Healthy males
|
9.0 ng/mL
STANDARD_DEVIATION 6.0 • n=20 Participants • Mean (SD) are given for baseline examination for 20 healthy males in protocol 1 and 2, and for 83 men and women with CAD in protocol 3.
|
|
tPA antigen
Coronary artery disease (CAD) patients
|
11.6 ng/mL
STANDARD_DEVIATION 4.5 • n=83 Participants • Mean (SD) are given for baseline examination for 20 healthy males in protocol 1 and 2, and for 83 men and women with CAD in protocol 3.
|
|
Leptin
Healthy males
|
4.7 ng/mL
STANDARD_DEVIATION 3.6 • n=20 Participants • Mean (SD) are given for baseline examination for 20 healthy males in protocol 1 and 2, and for 83 men and women with CAD in protocol 3.
|
|
Leptin
Coronary artery disease (CAD) patients
|
13.2 ng/mL
STANDARD_DEVIATION 7.5 • n=83 Participants • Mean (SD) are given for baseline examination for 20 healthy males in protocol 1 and 2, and for 83 men and women with CAD in protocol 3.
|
|
Systolic Blood Pressure
Healthy males
|
139 mmHg
STANDARD_DEVIATION 14.2 • n=20 Participants • Mean (SD) are given for baseline examination for 20 healthy males in protocol 1 and 2, and for 83 men and women with CAD in protocol 3.
|
|
Systolic Blood Pressure
Coronary artery disease (CAD) patients
|
130 mmHg
STANDARD_DEVIATION 18 • n=83 Participants • Mean (SD) are given for baseline examination for 20 healthy males in protocol 1 and 2, and for 83 men and women with CAD in protocol 3.
|
|
Heart rate
Healthy males
|
56 Beats per minute (SEM)
STANDARD_DEVIATION 5.9 • n=20 Participants • Mean (SD) are given for baseline examination for 20 healthy males in protocol 1 and 2, and for 83 men and women with CAD in protocol 3.
|
|
Heart rate
Coronary artery disease (CAD) patients
|
57 Beats per minute (SEM)
STANDARD_DEVIATION 11 • n=83 Participants • Mean (SD) are given for baseline examination for 20 healthy males in protocol 1 and 2, and for 83 men and women with CAD in protocol 3.
|
PRIMARY outcome
Timeframe: 18 minutes in protocol 1, 3 hours in protocol 2, non-applicable (NA) in protocol 3The primary outcome in all protocols were local blood-flow in the forearm (FBF). This was measured by venous occlusion plethysmography using mercury-in-silastic strain gauges and the unit is mL/100mL of tissue/min. In protocol 1, the FBF response to increasing levels of leptin was evaluated, In protocol 2, the FBF response to vasodilators on top of leptin or saline infusion was evaluated, and in protocol 3, FBF was measured after infusion of vasodilators and no leptin was given.
Outcome measures
| Measure |
Leptin Infusion, no Saline Given
n=10 Participants
In protocol 1, leptin was infused and blood-flow (FBF) was measured.
|
Leptin Plus Vasodilators
n=10 Participants
In protocol 2, leptin or saline was infused in the forearm which was followed by infusion of vasodilators. Blood flow (FBF) was measured.
|
Vasodilators in CAD Patients
n=83 Participants
Blood flow was measured locally in the forearm (FBF) after infusion of vasodilators. No leptin was given.
|
|---|---|---|---|
|
Forearm Blood-flow (FBF)
Leptin infused
|
1.75 ml/100 mg tissue/min
Standard Error 0.14
|
3.1 ml/100 mg tissue/min
Standard Error 0.4
|
NA ml/100 mg tissue/min
Standard Error NA
Leptin not infused.
|
|
Forearm Blood-flow (FBF)
Saline infused
|
NA ml/100 mg tissue/min
Standard Error NA
Saline not infused
|
3.4 ml/100 mg tissue/min
Standard Error 0.4
|
NA ml/100 mg tissue/min
Standard Error NA
Saline not infused
|
SECONDARY outcome
Timeframe: 18 minutes in protocol 1, 3 hours in protocol 2, NA in protocol 3In all protocols, fibrinolytic variables were measured. In protocol 2 and 3, in the infused forearm after vasodilatation with bradykinin or substance P, respectively. The fibrinolytic variable measured in all protocols was tPA activity (IU/mL) and is reported here after the leptin infusion, when applicable.
Outcome measures
| Measure |
Leptin Infusion, no Saline Given
n=10 Participants
In protocol 1, leptin was infused and blood-flow (FBF) was measured.
|
Leptin Plus Vasodilators
n=10 Participants
In protocol 2, leptin or saline was infused in the forearm which was followed by infusion of vasodilators. Blood flow (FBF) was measured.
|
Vasodilators in CAD Patients
n=83 Participants
Blood flow was measured locally in the forearm (FBF) after infusion of vasodilators. No leptin was given.
|
|---|---|---|---|
|
Release of Fibrinolytic Variables (Tissue Plasminogen Activator [tPA] and Plasminogen Activator Inhibitor-1 [PAI-1])
Leptin infused
|
0.56 IU/mL
Standard Error 0.12
|
0.91 IU/mL
Standard Error 0.38
|
NA IU/mL
Standard Error NA
Leptin not infused
|
|
Release of Fibrinolytic Variables (Tissue Plasminogen Activator [tPA] and Plasminogen Activator Inhibitor-1 [PAI-1])
Saline infused
|
NA IU/mL
Standard Error NA
Saline not infused
|
0.73 IU/mL
Standard Error 0.26
|
NA IU/mL
Standard Error NA
Saline not infused
|
SECONDARY outcome
Timeframe: 18 minutes in protocol 1, 3 hours in protocol 2, NA in protocol 3Population: In arm 3, the participants were not given any leptin, endogenous leptin was measured
Plasma leptin concentration (ng/mL) was measured in all protocols, and in protocol 1 and 2, specifically in both infused and in non-infused arms. Data given are leptin concentrations in the infused arm at the end of the infusion.
Outcome measures
| Measure |
Leptin Infusion, no Saline Given
n=10 Participants
In protocol 1, leptin was infused and blood-flow (FBF) was measured.
|
Leptin Plus Vasodilators
n=10 Participants
In protocol 2, leptin or saline was infused in the forearm which was followed by infusion of vasodilators. Blood flow (FBF) was measured.
|
Vasodilators in CAD Patients
n=83 Participants
Blood flow was measured locally in the forearm (FBF) after infusion of vasodilators. No leptin was given.
|
|---|---|---|---|
|
Leptin
Leptin infused
|
186.2 ng/mL
Standard Error 10.2
|
13.1 ng/mL
Standard Error 3.4
|
NA ng/mL
Standard Error NA
Leptin was not infused
|
|
Leptin
Saline infused
|
NA ng/mL
Standard Error NA
Saline not infused
|
3.4 ng/mL
Standard Error 1.2
|
NA ng/mL
Standard Error NA
Saline not infused
|
SECONDARY outcome
Timeframe: 18 minutes in protocol 1, 3 hours in protocol 2, NA in protocol 3In all protocols, blood pressure (mmHg) was measured concomitantly using a semi-automated non-invasive sphygmomanometer. Systolic blood pressure is reported here after leptin or saline infusion, when applicable.
Outcome measures
| Measure |
Leptin Infusion, no Saline Given
n=10 Participants
In protocol 1, leptin was infused and blood-flow (FBF) was measured.
|
Leptin Plus Vasodilators
n=10 Participants
In protocol 2, leptin or saline was infused in the forearm which was followed by infusion of vasodilators. Blood flow (FBF) was measured.
|
Vasodilators in CAD Patients
n=83 Participants
Blood flow was measured locally in the forearm (FBF) after infusion of vasodilators. No leptin was given.
|
|---|---|---|---|
|
Systolic Blood Pressure
Leptin infused
|
140 mmHg
Standard Error 3.7
|
134 mmHg
Standard Error 3.3
|
NA mmHg
Standard Error NA
Leptin was not infused
|
|
Systolic Blood Pressure
Saline infused
|
NA mmHg
Standard Error NA
Saline not infused
|
136 mmHg
Standard Error 2.9
|
NA mmHg
Standard Error NA
Saline not infused
|
SECONDARY outcome
Timeframe: 18 minutes in protocol 1, 3 hours in protocol 2, NA in protocol 3In all protocols, heart rate (beats per minute) was measured concomitantly. Heart rate is reported here after leptin or saline infusion, when applicable.
Outcome measures
| Measure |
Leptin Infusion, no Saline Given
n=10 Participants
In protocol 1, leptin was infused and blood-flow (FBF) was measured.
|
Leptin Plus Vasodilators
n=10 Participants
In protocol 2, leptin or saline was infused in the forearm which was followed by infusion of vasodilators. Blood flow (FBF) was measured.
|
Vasodilators in CAD Patients
n=83 Participants
Blood flow was measured locally in the forearm (FBF) after infusion of vasodilators. No leptin was given.
|
|---|---|---|---|
|
Heart Rate
Leptin infused
|
59 Beats per minute
Standard Error 1.5
|
66 Beats per minute
Standard Error 3.6
|
NA Beats per minute
Standard Error NA
Leptin not infused
|
|
Heart Rate
Saline infused
|
NA Beats per minute
Standard Error NA
Saline not infused
|
66 Beats per minute
Standard Error 2.6
|
NA Beats per minute
Standard Error NA
Saline not infused
|
Adverse Events
Leptin Infusion
Leptin Infusion Plus Vasodilator Infusion
Saline Infusion Plus Vasodilator Infusion
Vasodilator Infusion in CAD Patients
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place