Prevention of Type 2 Diabetes Mellitus by L-Arginine in Patients With Metabolic Syndrome (L-arginine)

This study has been completed.
Sponsor:
Information provided by:
IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT00917449
First received: June 9, 2009
Last updated: NA
Last verified: June 2009
History: No changes posted
  Purpose

Aim

The principal objective of this project is:

• To evaluate the efficacy of long term (18 months) L-Arginine therapy in preventing or delaying clinical onset of type 2 diabetes mellitus in subjects with impaired glucose tolerance (IGT) and Metabolic Syndrome.

Secondary end points are:

  1. To define if a long term treatment with L-arginine is able to ameliorate insulin sensitivity and endothelial dysfunction in this population.
  2. To find new risk profiles and candidate genes able to define the sub-group of patients at higher risk to develop type 2 diabetes mellitus.

Methodology This is a double blind, parallel, one centre study to determine if long term oral L-arginine administration is able to delay or prevent type 2 diabetes mellitus in patients with Metabolic Syndrome. Two hundred and ninety four subjects were recruited at the Cardio-Metabolic and Clinical Trials Unit of the San Raffaele Scientific Institute. One hundred and forty two patients were randomized to enter the study and assigned to two arms: oral L-arginine (6.4 g/die) or placebo, in addition to diet and physical exercise. The treatment were maintained for 18 months. Visits were performed every 3 months for clinical evaluation, blood samples, treatment supply and collection of data on adverse events. Furthermore, patients were contacted every month by telephone to evaluate the accurate continuation of the study and they were instructed to phone to the centre in case of possible adverse events.

An OGTT were performed before the enter into the study and at the end of the study period. An additional OGTT were performed at an intermediate visit if fasting glucose levels were more than 126 mg/dl. A diabetic response caused the end-point of the patient. Metabolic, hormonal and endothelial activation and inflammation parameters were measured. Evaluation of endothelium-mediated and non-endothelium-mediated vasodilatation were performed by strain gauche plethysmography evaluating forearm blood at the basal state. in post-ischemic conditions and after nitroglycerine administration.

Before the enter into the study, an additional blood sample were drawn for DNA extraction and candidate genes variants evaluation. Before the enter into the study and at the end of the study period, gene expression for inflammation were measured on mRNA extraction on endothelial progenitor cells.


Condition Intervention Phase
Metabolic Syndrome
Impaired Glucose Tolerance
Insulin Resistance
Endothelial Dysfunction
Drug: L-arginine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Interventional Pharmacological Study With L-Arginine in the Prevention of Type 2 Diabetes Mellitus in Patients With Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • To evaluate the efficacy of long term (18 months) L-Arginine therapy in preventing or delaying clinical onset of type 2 diabetes mellitus in subjects with impaired glucose tolerance (IGT) and Metabolic Syndrome. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Define if the treatment with L-arginine can ameliorate insulin sensitivity and endothelial dysfunction and find new risk profiles and candidate genes able to characterize the sub-group of patients at higher risk to develop type 2 diabetes mellitus. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 142
Study Start Date: December 2005
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: L-arginine
L-arginine (3.2 gr bid) plus lifestyle counselling vs placebo plus lifestyle counselling
Drug: L-arginine
Oral L-arginine (3.2 gr bid)for 18 months
Other Name: bioarginine
Placebo Comparator: placebo
placebo plus lifestyle counselling for 18 months
Drug: Placebo
Oral Placebo BID for 18 months
Other Name: placebo

Detailed Description:

This is a double blind, parallel, one centre study to determine if long term oral L-arginine administration is able to delay or prevent type 2 diabetes mellitus in patients with IGT and Metabolic Syndrome. Two hundred and ninety four subjects were recruited at the CardioMetabolic and Clinical Trials Unit of the San Raffaele Scientific Institute. One hundred and fourty two patients were randomized to enter the study. Patients were randomly assigned to two arms: oral L-arginine (6.4 g/die) or placebo in blind scheme. The treatment were maintained for 18 months. Visits will be performed every 3 months for clinical evaluation, blood samples, treatment supply and collect data on adverse events, if any. Furthermore, patients were contacted every month by telephone to evaluate the accurate continuation of the study and they were instructed to phone to the centre in case of possible adverse events.

Inclusion criteria

  • Written informed consent must be obtained before any procedure of the study is done.
  • Male or Female aged more than 35 years.
  • Diagnosis of IGT after a standard Glucose Tolerance Test (OGTT, 75 g)
  • Moreover, in order to be considered affected by Metabolic Syndrome, they must have two or more of the following criteria:
  • Abdominal obesity (waist>120 cm for man, >88 cm for women)
  • Hypertriglyceridemia (>150 mg/dl)
  • Low HDL cholesterol (<40mg/dl in man, <50 mg/dl in woman)
  • Hypertension (>130 / >85 mmHg) Exclusion criteria
  • Presence of type 1 or type 2 diabetes mellitus
  • Fasting glucose levels >126 mg/dl
  • Sitting Systolic Arterial Pressure >140mmHg, and Sitting Diastolic Arterial Pressure >90mmHg
  • Pregnancy
  • Known renal insufficiency or creatinine levels more than 1.8 mg/dl,
  • Presence of chronic hepatopathy or levels of ALT and AST more than two standard deviations from normality levels
  • Presence of malignancy
  • Abuse of alcohol or abuse substances
  • Psychiatric disorders
  Eligibility

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent must be obtained before any procedure of the study is done.
  • Male or Female aged more than 35 years.
  • Diagnosis of IGT after a standard Glucose Tolerance Test (OGTT, 75 g)
  • Moreover, in order to be considered affected by Metabolic Syndrome, they must have two or more of the following criteria:
  • Abdominal obesity (waist>120 cm for man, >88 cm for women)
  • Hypertriglyceridemia (>150 mg/dl)
  • Low HDL cholesterol (<40mg/dl in man, <50 mg/dl in woman)
  • Hypertension (>130 / >85 mmHg)

Exclusion Criteria:

  • Presence of type 1 or type 2 diabetes mellitus
  • Fasting glucose levels >126 mg/dl
  • Sitting Systolic Arterial Pressure >140mmHg, and Sitting Diastolic Arterial Pressure >90mmHg
  • Pregnancy
  • Known renal insufficiency or creatinine levels more than 1.8 mg/dl,
  • Presence of chronic hepatopathy or levels of ALT and AST more than two standard deviations from normality levels
  • Presence of malignancy
  • Abuse of alcohol or abuse substances
  • Psychiatric disorders
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00917449

Locations
Italy
Scientific Institute San Raffaele
Milan, Italy, 20132
Sponsors and Collaborators
IRCCS San Raffaele
Investigators
Principal Investigator: PierMarco Piatti, MD Scientific Institute San Raffaele
  More Information

No publications provided

Responsible Party: Piatti PierMarco, San Raffaele Scientific Institute
ClinicalTrials.gov Identifier: NCT00917449     History of Changes
Other Study ID Numbers: 2005-004639-24
Study First Received: June 9, 2009
Last Updated: June 9, 2009
Health Authority: Italy: Ministry of Health

Keywords provided by IRCCS San Raffaele:
Metabolic Syndrome
Impaired glucose tolerance
Type 2 diabetes mellitus
Endothelial dysfunction
L-arginine
Insulin resistance

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Insulin Resistance
Glucose Intolerance
Metabolic Syndrome X
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperinsulinism
Hyperglycemia

ClinicalTrials.gov processed this record on July 29, 2014