Arginase Inhibition in Type 1 and Type 2 Diabetes Mellitus

Sponsor

Karolinska Institutet (Other)

Overall Status

Recruiting

CT.gov ID

NCT05806502

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the efficacy of arginase inhibition on endothelial function in patients with type 1 diabetes and type 2 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Type 2 Diabetes	Diagnostic Test: Nω-hydroxy-nor-arginine	N/A

Detailed Description

Detailed Description:

The study is performed on one group of patients with type 1 diabetes and one group of patients with type 2 diabetes.

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.

Twelve subjects are included in each group. 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

The Effect of Arginase Inhibition on Vascular Endothelial Function in Patients With Type 1 and Type 2 Diabetes

Actual Study Start Date :

Nov 1, 2018

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Type 1 diabetes Endothelium-dependent and -independent vasodilatation before and after 120 min intra-arterial administration of arginase the inhibitor N-omega-hydroxy-nor-l-arginine (nor-NOHA).	Diagnostic Test: Nω-hydroxy-nor-arginine Arginase inhibitor
Experimental: Type 2 diabetes Endothelium-dependent and -independent vasodilatation before and after 120 min intra-arterial administration of arginase the inhibitor N-omega-hydroxy-nor-l-arginine (nor-NOHA).	Diagnostic Test: Nω-hydroxy-nor-arginine Arginase inhibitor

Arm

Intervention/Treatment

Experimental: Type 1 diabetes

Endothelium-dependent and -independent vasodilatation before and after 120 min intra-arterial administration of arginase the inhibitor N-omega-hydroxy-nor-l-arginine (nor-NOHA).

Diagnostic Test: Nω-hydroxy-nor-arginine

Arginase inhibitor

Experimental: Type 2 diabetes

Endothelium-dependent and -independent vasodilatation before and after 120 min intra-arterial administration of arginase the inhibitor N-omega-hydroxy-nor-l-arginine (nor-NOHA).

Diagnostic Test: Nω-hydroxy-nor-arginine

Arginase inhibitor

Outcome Measures

Primary Outcome Measures

Endothelium-dependant increase in forearm blood flow [120 minutes]
Change in forearm blood flow

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Type 1 diabetes
Type 2 diabetes

Exclusion Criteria:

Age >80 years
Acute coronary or ischemic event during the last three months
Vascular surgery of the arm
Peripheral vascular disease affecting the arm
Ongoing anticoagulant medication
Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Karolinska Institutet	Stockholm		Sweden	17176

Sponsors and Collaborators

Karolinska Institutet

Investigators

Principal Investigator: John Pernow, MD, Karolinska Institutet

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

John Pernow, Principal investigator, Karolinska Institutet

ClinicalTrials.gov Identifier:

NCT05806502

Other Study ID Numbers:

T1DM study

First Posted:

Apr 10, 2023

Last Update Posted:

Apr 11, 2023

Last Verified:

Apr 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Diabetes Mellitus

Diabetes Mellitus, Type 2

Study Results

No Results Posted as of Apr 11, 2023