Arginase Inhibition in Humans With Obesity

Obese Clinical Trial

Official title:

Arginase Inhibition and Endothelial Function in Humans With Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05536934
• Other study ID #: 2016/1173-32
• Status: Completed
• Phase: Early Phase 1
• Start date: December 2016
• Est. completion date: March 2022

Study information

• Verified date: September 2022
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the efficacy of arginase inhibition on endothelial function in humans with obesity.

Description:

The study is performed on one group of subjects with body mass index >35 and the absence of type 2 diabetes.

Inclusion criteria:

Body mass index >35 kg/m2.

Exclusion criteria:

Age >80 years. Type 2 diabetes defined as >7 mmol/L in fasting plasma glucose or >11 mmol/L following 2h of oral glycemic load.

Myocardial infarction/unstable angina within 6 weeks prior to the study. Treatment with oral anticoagulants (Warfarin or New oral anticoagulants), Raynaud's phenomenon, peripheral vasculopathies, arterial shunting or other vascular surgery of the study arm.

Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol.

Participant in an ongoing study. Unwillingness to participate following oral and written information.

Forearm blood flow is determined by venous occlusion plethysmography. Endothelium-dependent vasodilatation is determined during intra-brachial artery infusion of serotonin (21, 70 and 210 ng/min). Endothelium-independent vasodilatation is determined by infusion of sodium nitroprusside (SNP; 1, 3 and 10 µg/min). Each dose is given for 2 min at a rate of 2.5 ml/min. Data are expressed as percentage change in forearm blood from baseline flow.

Fifteen subjects are included. On the day of the study the subject arrives to the laboratory after having a light breakfast. Forearm vessels of the non-dominant arm are cannulated and forearm blood flow is determined as described above. Baseline endothelium-dependent and endothelium-independent vasodilatation is determined by intra-arterial infusions of serotonin and SNP, respectively. Thereafter an intra-arterial infusion of the arginase inhibitor N-omega-hydroxy-nor-l-arginine (nor-NOHA) is administered as an intra-arterial infusion at a rate of 0.1 mg/min and is maintained for 120 min. The dose is based on a previous study by our group demonstrating improved endothelial function. Endothelium-dependent and -independent vasodilatation is reassessed at 120 min of infusion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: March 2022
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

BMI >35kg/m2

Exclusion Criteria:

Age >80 years. Type 2 diabetes defined as >7 mmol/L in fasting plasma glucose or >11 mmol/L following 2h of oral glycemic load.

Myocardial infarction/unstable angina within 6 weeks prior to the study. Treatment with oral anticoagulants (Warfarin or New oral anticoagulants), Raynaud's phenomenon, peripheral vasculopathies, arterial shunting or other vascular surgery of the study arm.

Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol.

Participant in an ongoing study. Unwillingness to participate following oral and written information.

Related Conditions & MeSH terms

• Endothelial Function
• Obese
• Obesity

Intervention

Drug:
• N?-hydroxy-nor-arginine

Locations

Country	Name	City	State
Sweden	Karolinska Institutet, Karolinska University Hospital	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endothelium-dependent change in forearm blood flow	Percentage change in forearm blood flow from baseline induced by the endothelium-dependent vasodilator serotonin during arginase blockade vs. saline.	120 min intraarterial infusion of the arginase inhibitor nor-NOHA
Secondary	Endothelium-independent change in forearm blood flow	Percentage change in forearm blood flow from baseline induced by the endothelium-independent vasodilator nitroprusside during arginase blockade vs. saline.	120 min intraarterial infusion of the arginase inhibitor nor-NOHA