Metabolic SyndromePhase 3L-arginineNCT00917449
Prevention of Type 2 Diabetes Mellitus by L-Arginine in Patients With Metabolic Syndrome
A Phase 3 study testing L-arginine in people with Metabolic Syndrome and Impaired Glucose Tolerance, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Metabolic Syndrome, Impaired Glucose Tolerance, Insulin Resistance
- What is being tested?
- L-arginine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 142 participants
- Where
- 1 siteItaly
- Study dates
- Dec 2005to Jun 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 9Show fewer
- Presence of malignancy
- Abuse of alcohol or abuse substances
- Psychiatric disorders
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Interventional Pharmacological Study With L-Arginine in the Prevention of Type 2 Diabetes Mellitus in Patients With Metabolic Syndrome
Aim
The principal objective of this project is:
Read more
- 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:
- To define if a long term treatment with L-arginine is able to ameliorate insulin sensitivity and endothelial dysfunction in this population.
- 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.
Read the 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
- Conditions
- Metabolic Syndrome, Impaired Glucose Tolerance, Insulin Resistance, Endothelial Dysfunction
- Being tested
- L-arginine, Placebo
- Keywords
- Metabolic Syndrome, Impaired glucose tolerance, Type 2 diabetes mellitus, Endothelial dysfunction, L-arginine, Insulin resistance
- Medical subject headings
- Metabolic Syndrome, Glucose Intolerance, Insulin Resistance, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-arginineDrug
Also called bioarginine
Oral L-arginine (3.2 gr bid)for 18 months
PlaceboDrug
Oral Placebo BID for 18 months
| Study group | Role | What they receive |
|---|---|---|
| L-arginine | Active comparator | L-arginine (3.2 gr bid) plus lifestyle counselling vs placebo plus lifestyle counselling Receives: Drug: L-arginine |
| placebo | Placebo comparator | placebo plus lifestyle counselling for 18 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 months
Secondary outcomes (1)
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.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2009 (estimated)
- Study startDec 2005
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Investigators
- PierMarco Piatti, MD, Principal investigator, Scientific Institute San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00917449
- Sponsor's protocol ID
- 2005-004639-24
- Other IDs
- 2005
- Acronym
- L-arginine
- Status last verified
- Jun 2009
- First submitted
- 9 Jun 2009
- Last updated
- 10 Jun 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Monti LD, Galluccio E, Villa V, Fontana B, Spadoni S, Piatti PM. Decreased diabetes risk over 9 year after 18-month oral L-arginine treatment in middle-aged subjects with impaired glucose tolerance and metabolic syndrome (extension evaluation of L-arginine study). Eur J Nutr. 2018 Dec;57(8):2805-2817. doi: 10.1007/s00394-017-1548-2. Epub 2017 Oct 20.
PubMed 29052766Monti LD, Galluccio E, Fontana B, Spadoni S, Comola M, Marrocco Trischitta MM, Chiesa R, Comi G, Bosi E, Piatti P. Pharmacogenetic influence of eNOS gene variant on endothelial and glucose metabolism responses to L-arginine supplementation: Post hoc analysis of the L-arginine trial. Metabolism. 2015 Nov;64(11):1582-91. doi: 10.1016/j.metabol.2015.08.015. Epub 2015 Aug 28.
PubMed 26385052
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interventional Pharmacological Study With L-Arginine in the Prevention of Type 2 Diabetes Mellitus in Patients With Metabolic Syndrome
- ClinicalTrials.gov ID
- NCT00917449
- Acronym / sponsor ID
- L-arginine / 2005-004639-24
- Conditions
- Metabolic Syndrome, Impaired Glucose Tolerance, Insulin Resistance, Endothelial Dysfunction
- Keywords
- Metabolic Syndrome, Impaired glucose tolerance, Type 2 diabetes mellitus, Endothelial dysfunction, L-arginine, Insulin resistance
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 142 participants (actual)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- Dec 2005
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 10 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To define if a long term treatment with L-arginine is able to ameliorate insulin sensitivity and endothelial dysfunction in this population.
- 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.
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
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-arginine | Active comparator | Drug: L-arginineL-arginine (3.2 gr bid) plus lifestyle counselling vs placebo plus lifestyle counselling |
| placebo | Placebo comparator | Drug: Placeboplacebo plus lifestyle counselling for 18 months |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (9 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-arginineAlso: bioarginineOral L-arginine (3.2 gr bid)for 18 months | Drug | L-arginine |
| PlaceboOral Placebo BID for 18 months | Drug | placebo |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2009.
- Derived from this study: PubMed 29052766Monti LD, Galluccio E, Villa V, Fontana B, Spadoni S, Piatti PM. Decreased diabetes risk over 9 year after 18-month oral L-arginine treatment in middle-aged subjects with impaired glucose tolerance and metabolic syndrome (extension evaluation of L-arginine study). Eur J Nutr. 2018 Dec;57(8):2805-2817. doi: 10.1007/s00394-017-1548-2. Epub 2017 Oct 20.
- Derived from this study: PubMed 26385052Monti LD, Galluccio E, Fontana B, Spadoni S, Comola M, Marrocco Trischitta MM, Chiesa R, Comi G, Bosi E, Piatti P. Pharmacogenetic influence of eNOS gene variant on endothelial and glucose metabolism responses to L-arginine supplementation: Post hoc analysis of the L-arginine trial. Metabolism. 2015 Nov;64(11):1582-91. doi: 10.1016/j.metabol.2015.08.015. Epub 2015 Aug 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
PierMarco Piatti, MD principal investigator
Scientific Institute San Raffaele
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing L-arginine in people with Metabolic Syndrome and Impaired Glucose Tolerance, run by IRCCS San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jun 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00917449, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2009.