DiabetesL-BIOARGNCT06686069
Effect of Oral L-arginine 3.32 g a Day on Oxidative Stress Influencing Beta Cell Function and Insulin Resistance.
A study testing bioarginina zero in people with Diabetes and Pre-diabetes, run by Federico II University.
Trial summary
The objective of this clinical trial is to explore whether L-arginine supplementation with 3.32g/day may enhance antioxidant defenses in overweight and obese patients with pre-diabetes and metabolic syndrome, possibly providing beta cell function and insulin resistance improvement. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes, Pre-diabetes, Metabolic Syndrome
- What is being tested?
- bioarginina zero
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- No sites listed yet
- Study dates
- 18 Jan 2025to 30 Dec 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- consented male and female patients aged 20-70 years with Body Mass Index (BMI) >25 kg/m2,
- pre-diabetes (fasting glucose 100-125 mg/dL and HbA1c 5.7-6.5%) or metabolic syndrome, defined according to modified NCEP-ATP III criteria (Grundy SM et al., Circulation, 2005) as the presence of three or more of the following clinical features: blood glucose levels >100 mg/dL, HDL-cholesterol <40 mg/dL in males and <50 mg/dL in females, triglycerides levels >150 mg/dL, waist circumference >102 cm in males and >88 cm in females and hypertension, defined as repeated blood pressure measurements >130/85 mmHg.
Who cannot join
- moderate to severe renal impairment (calculated creatinine clearance (CrCl) <60 mL/min according to the Cockcroft-Gault formula);
- hepatic dysfunction (ALT/AST >3 x upper limit of normal and total bilirubin >3 mg/dL);
- hypoalbuminemia (serum albumin <3 g/dL);
- history of any past or current clinically significant cardiovascular diseases;
- monogenic, secondary and pharmacological causes of diabetes and obesity;
- any other clinical condition/disease that the Principal Investigator believes might confound study outcome;
- patients on treatment with insulin or any anti-diabetic drugs or medications known to influence glucose tolerance will also be excluded;
- pregnant or breast-feeding women.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Effect of Oral L-arginine 3.32 g a Day on Oxidative Stress Influencing Beta Cell Function and Insulin Resistance. A Phase 3, Randomized, Double-blind, Placebo-controlled Explorative Study in Overweight and Obese Patients With Pre-diabetes.
The objective of this clinical trial is to explore whether L-arginine supplementation with 3.32g/day may enhance antioxidant defenses in overweight and obese patients with pre-diabetes and metabolic syndrome, possibly providing beta cell function and insulin resistance improvement. The primary efficacy endpoint will be to explore the effects of a short-term L-arginine supplementation on AOPP levels and PAI after three months of treatment, based on the rationale explained above. Secondary, the effects of L-arginine supplementation on lipid peroxidation products and antioxidant defenses will be explored. Tertiary, the effects of L-arginine supplementation on insulin resistance and glucose metabolism parameters will be also evaluated.
Read the detailed description
Recent studies have demonstrated beneficial effects of the use of L-arginine supplementation as a nutrient treatment in diabetes and prediabetes, with documented beneficial effects on β- cell function and insulin sensitivity .
A long-term follow-up randomized clinical trial also demonstrated a reduced cumulative incidence of type 2 diabetes among subjects at high risk of developing the disease . The same study reported a significantly AOPP levels reduction at 18 months in L-arginine arm compared to placebo and this effect was maintained through the 108 months of follow up. Indeed, AOPP levels decreased by 26.1% at 18 months, remaining lower during the post intervention period in L-arginine group.
However, in this study, AOPP levels were firstly evaluated at baseline and then only 18 months after starting treatment. Therefore, to date, no data are currently available regarding the effects of a short-term treatment on AOPPs levels. In addition, data in vivo on rats suggest a rapid improvement in antioxidant defense and in total antioxidative capacity in plasma and liver after a 14 days treatment period with L-arginine.
Advanced oxidation protein products are formed during oxidative stress by myeloperoxidase action in activated neutrophils through chloraminated oxidants production. AOPPs molecular structure is similar to advanced glycation endproducts (AGEs) as they have similar biological activities. Precisely, AOPPs exert induction of proinflammatory cytokines and adhesion molecules maintaining inflammatory pathways activated and favoring pro-oxidant state. In addition, many reports highlighted a strict correlation between AOPPs and glucose metabolism suggesting being an early marker of diabetes mellitus and metabolic syndrome. The prooxidant-antioxidant index (PAI) has been proposed as possible marker of MetS. It is expressed as the ratio between the AOPP levels and the total radical-trapping antioxidant capacity (TRAP), a surrogate for the total antioxidant defenses in the plasma. An interesting study by Venturini et al. evidenced the relationship between AOPPs and MetS also highlighting that PAI progressively increased (P <0.05) according to the number of MetS components, whereas AOPPs and total radical-trapping antioxidant parameter increased (P <0.05) when 5 components were compared with 3 and 4 components .
Lipid peroxidation products such as malondialdehyde (MDA), and 4-hydroxynonenal (HNE) have been reported to be highly related to inflammation and MetS. These molecules are considered important biomarkers of oxidative stress because of the high susceptibility of polyunsaturated fatty acids-rich cell membranes to lipid peroxidation when exposed to ROS or other free radicals . A positive correlation has been described by several studies among obesity, IR, MetS, glycaemic control and MDA and HNE levels.
Regarding the antioxidant enzymes, a study by Lang et al. on rats fed with L-arginine for 14 days demonstrated a significant stimulation in GSH synthesis enzymes, CAT, SOD and GPx activity and mRNA expression enhancing the total antioxidative capacity in plasma (T-AOC or TRAP) and in the liver strongly suggesting that L-arginine oral administration can ameliorate antioxidant defenses.
To conduct this study, the investigators selected a L-arginine dosage of 3,32 g/day, based on evidence that this dosage was associated to an improvement of the inflammatory response and beneficial modulating of oxidative stress in favor of an antioxidant state.
- Conditions
- Diabetes, Pre-diabetes, Metabolic Syndrome
- Being tested
- bioarginina zero, Placebo
- Keywords
- L-bioarginine
- Medical subject headings
- Diabetes Mellitus, Glucose Intolerance, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bioarginina zeroDietary supplement
treatment
PlaceboDietary supplement
absence of treatment
| Study group | Role | What they receive |
|---|---|---|
| placebo, untreated | Placebo comparator | No treatment Receives: Dietary Supplement: bioarginina zero; Dietary Supplement: Placebo |
| bioarginina zero | Active comparator | L-arginine treatment Receives: Dietary Supplement: bioarginina zero; Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
effects of a short-term L-arginine supplementation on AOPP levels after three months of treatment
effects of a short-term L-arginine supplementation on AOPP levels and PAI after three months of treatment
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2024
- Study start18 Jan 2025 (estimated)
- Primary completion18 Nov 2025 (estimated)
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by Federico II UniversityThe 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Treatment with L-arginine vs placebo
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federico II University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Barbara Maglione, Federico II University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06686069
- Sponsor's protocol ID
- 180893
- Other IDs
- 1893
- Acronym
- L-BIOARG
- Status last verified
- Nov 2024
- First submitted
- 5 Nov 2024
- Last updated
- 13 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Oral L-arginine 3.32 g a Day on Oxidative Stress Influencing Beta Cell Function and Insulin Resistance. A Phase 3, Randomized, Double-blind, Placebo-controlled Explorative Study in Overweight and Obese Patients With Pre-diabetes.
- ClinicalTrials.gov ID
- NCT06686069
- Acronym / sponsor ID
- L-BIOARG / 180893
- Conditions
- Diabetes, Pre-diabetes, Metabolic Syndrome
- Keywords
- L-bioarginine
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Federico II UniversityUniversity, hospital or other
- Study start
- 18 Jan 2025 (estimated)
- Primary completion
- 18 Nov 2025 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 13 Nov 2024 (actual)
- 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.
The objective of this clinical trial is to explore whether L-arginine supplementation with 3.32g/day may enhance antioxidant defenses in overweight and obese patients with pre-diabetes and metabolic syndrome, possibly providing beta cell function and insulin resistance improvement. The primary efficacy endpoint will be to explore the effects of a short-term L-arginine supplementation on AOPP levels and PAI after three months of treatment, based on the rationale explained above. Secondary, the effects of L-arginine supplementation on lipid peroxidation products and antioxidant defenses will be explored. Tertiary, the effects of L-arginine supplementation on insulin resistance and glucose metabolism parameters will be also evaluated.
Detailed description
Recent studies have demonstrated beneficial effects of the use of L-arginine supplementation as a nutrient treatment in diabetes and prediabetes, with documented beneficial effects on β- cell function and insulin sensitivity .
A long-term follow-up randomized clinical trial also demonstrated a reduced cumulative incidence of type 2 diabetes among subjects at high risk of developing the disease . The same study reported a significantly AOPP levels reduction at 18 months in L-arginine arm compared to placebo and this effect was maintained through the 108 months of follow up. Indeed, AOPP levels decreased by 26.1% at 18 months, remaining lower during the post intervention period in L-arginine group.
However, in this study, AOPP levels were firstly evaluated at baseline and then only 18 months after starting treatment. Therefore, to date, no data are currently available regarding the effects of a short-term treatment on AOPPs levels. In addition, data in vivo on rats suggest a rapid improvement in antioxidant defense and in total antioxidative capacity in plasma and liver after a 14 days treatment period with L-arginine.
Advanced oxidation protein products are formed during oxidative stress by myeloperoxidase action in activated neutrophils through chloraminated oxidants production. AOPPs molecular structure is similar to advanced glycation endproducts (AGEs) as they have similar biological activities. Precisely, AOPPs exert induction of proinflammatory cytokines and adhesion molecules maintaining inflammatory pathways activated and favoring pro-oxidant state. In addition, many reports highlighted a strict correlation between AOPPs and glucose metabolism suggesting being an early marker of diabetes mellitus and metabolic syndrome. The prooxidant-antioxidant index (PAI) has been proposed as possible marker of MetS. It is expressed as the ratio between the AOPP levels and the total radical-trapping antioxidant capacity (TRAP), a surrogate for the total antioxidant defenses in the plasma. An interesting study by Venturini et al. evidenced the relationship between AOPPs and MetS also highlighting that PAI progressively increased (P <0.05) according to the number of MetS components, whereas AOPPs and total radical-trapping antioxidant parameter increased (P <0.05) when 5 components were compared with 3 and 4 components .
Lipid peroxidation products such as malondialdehyde (MDA), and 4-hydroxynonenal (HNE) have been reported to be highly related to inflammation and MetS. These molecules are considered important biomarkers of oxidative stress because of the high susceptibility of polyunsaturated fatty acids-rich cell membranes to lipid peroxidation when exposed to ROS or other free radicals . A positive correlation has been described by several studies among obesity, IR, MetS, glycaemic control and MDA and HNE levels.
Regarding the antioxidant enzymes, a study by Lang et al. on rats fed with L-arginine for 14 days demonstrated a significant stimulation in GSH synthesis enzymes, CAT, SOD and GPx activity and mRNA expression enhancing the total antioxidative capacity in plasma (T-AOC or TRAP) and in the liver strongly suggesting that L-arginine oral administration can ameliorate antioxidant defenses.
To conduct this study, the investigators selected a L-arginine dosage of 3,32 g/day, based on evidence that this dosage was associated to an improvement of the inflammatory response and beneficial modulating of oxidative stress in favor of an antioxidant state.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Treatment with L-arginine vs placebo
| Arm | Type | Receives |
|---|---|---|
| placebo, untreated | Placebo comparator | Dietary Supplement: bioarginina zero, Dietary Supplement: PlaceboNo treatment |
| bioarginina zero | Active comparator | Dietary Supplement: bioarginina zero, Dietary Supplement: PlaceboL-arginine treatment |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- consented male and female patients aged 20-70 years with Body Mass Index (BMI) >25 kg/m2,
- pre-diabetes (fasting glucose 100-125 mg/dL and HbA1c 5.7-6.5%) or metabolic syndrome, defined according to modified NCEP-ATP III criteria (Grundy SM et al., Circulation, 2005) as the presence of three or more of the following clinical features: blood glucose levels >100 mg/dL, HDL-cholesterol <40 mg/dL in males and <50 mg/dL in females, triglycerides levels >150 mg/dL, waist circumference >102 cm in males and >88 cm in females and hypertension, defined as repeated blood pressure measurements >130/85 mmHg.
Key exclusion criteria (8 listed)
- moderate to severe renal impairment (calculated creatinine clearance (CrCl) <60 mL/min according to the Cockcroft-Gault formula);
- hepatic dysfunction (ALT/AST >3 x upper limit of normal and total bilirubin >3 mg/dL);
- hypoalbuminemia (serum albumin <3 g/dL);
- history of any past or current clinically significant cardiovascular diseases;
- monogenic, secondary and pharmacological causes of diabetes and obesity;
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 |
|---|---|---|
| bioarginina zerotreatment | Dietary supplement | bioarginina zero, placebo, untreated |
| Placeboabsence of treatment | Dietary supplement | bioarginina zero, placebo, untreated |
Primary outcome
effects of a short-term L-arginine supplementation on AOPP levels after three months of treatment
Time frame: 3 months
effects of a short-term L-arginine supplementation on AOPP levels and PAI after three months of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2024.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A study testing bioarginina zero in people with Diabetes and Pre-diabetes, run by Federico II University.
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 2 inclusion and 8 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: opening soon, as of the sponsor's last update on 13 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact barbara maglione, Master degree (3343293357, barbara.maglione@farmadamor.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
effects of a short-term L-arginine supplementation on AOPP levels after three months of treatment (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Nov 2024.