Health Subjects With Cardiovascular Risk Factors Clinical Trial
Official title:
Medium Term Effect of Sublingual L-glutathione (L-GSH) Supplementation on Flow Mediated Dilation and Oxidative Stress Markers in Male Subjects With Smoking Habit and/or Arterial Hypertension
| Verified date | May 2014 |
| Source | Niguarda Hospital |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | Italy: Ministry of Health |
| Study type | Interventional |
Background. The antioxidant systems are the main endogenous defense against free radicals,
and glutathione seems to play an important role in this mechanism. Reduced glutathione
enters into the detoxification processes of endogenous products, such as hydro- and
lipoperoxides and exogenous compounds such as pollutants, heavy metals and some drugs.
Changes in GSH homeostasis have been implicated in the etiology and progression of several
diseases. Supplementation of GSH may improve the endogenous antioxidant defense and may
contribute to decrease of oxidants tissue damage a pathophysiologic mechanism of many acute
and chronic diseases.
However, the efficacy of GSH treatment seems to be closely related to the degree of its
absorption and to the increase of its concentrations in plasma and cells. Previous studies
of oral GSH administration in healthy volunteers or in patients failed to find any effect in
terms of oxidative stress reduction and/or disease improvement because the GSH is quickly
catabolized by gastrointestinal tract. We have recently observed (preliminary data) that a
new sublingual formulation of L-GSH (OXITION), produced by PH&T S.r.l., is able to increase
erythrocyte and plasma GSH levels in healthy volunteers bypassing gastrointestinal barrier.
Objectives. The primary study objective is to determine whether medium term (4 weeks) of
sublingual L-GSH supplementation to a population with smoking habit and/or arterial
hypertension may result in improved endothelial function as assessed by the flow mediated
dilation (FMD) technique versus placebo. FMD is a surrogate end point validated in the
literature as prognostic predictor for major cardiovascular events in patients with
endothelial dysfunction. Secondary study objectives are to determine differences between the
2 treatment in terms of oxidative stress markers.
Methods. This is a phase 3, double-blind, randomized, placebo-controlled, cross-over study
performed in only one centre. Sixteen male subjects, aged ≥ 40 and ≤ 60 years, with smoking
habit and/or hypertension defined as arterial blood pressure ≥ 140 and/or 90 mmHg or in
anti-hypertensive treatment, will be enrolled and randomized to receive sublingual L-GSH
(100 mg twice a day) or placebo according to a double-blind cross-over design for 4 weeks
with a 3-week wash-out period between the two treatments. Baseline and at the end of each
treatment period, FMD assessment and blood samples collection for routine (creatinine, urea,
AST, ALT GGT, total cholesterol, HDL, LDL, triglycerides, fasting glucose) and specific
(aminothiols, nitrotyrosine, malondialdehyde, 8-hydroxy-deoxyguanine) biochemical
determination will be performed.
| Status | Completed |
| Enrollment | 16 |
| Est. completion date | May 2014 |
| Est. primary completion date | May 2014 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Male |
| Age group | 40 Years to 60 Years |
| Eligibility |
Inclusion Criteria: - informed consensus - age from 40 to 60 years, - without any signs or symptoms of cardio-cerebro-vascular event at the enrolment, - smokers (>10 cigarette/die from almost 1 year) - arterial hypertension (PAS=140 mmHg and/or PAD=90 mmHg or in anti-hypertensive treatment) Exclusion Criteria: - chronic assumption of acetylsalicylic acid and/or statins - obesity defined as BMI =30 kg/m2 - diabetes mellitus defined as fasting glycemia >126 mg/dL - dyslipidemia defined as LDL >155 mg/dL - chronic renal dysfunction with Glomerular Filtration Rate<60 mL/min/1.73 m2 - in acetylcysteine treatment or with any other GSH-related molecules supplementation - in vitamins supplementation or with other compounds derived from red rice (ARMOLIPID or similar). |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Italy | Oberdan Parodi, MD | Milan |
| Lead Sponsor | Collaborator |
|---|---|
| Niguarda Hospital |
Italy,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Adverse events | The safety will be assessed by monitoring the adverse effects related with the administration of LGSH or placebo | after 4, 8 and 12 weeks from the first visit V0 | Yes |
| Primary | endothelium-dependent vasodilation | Registration of pulsatile blood volume in the fingertips of both hands will be assessed by a non invasive plethysmographic method (Endo-PAT2000, Itamar Medical Ltd., Caesarea, Israel) system. Endo-PAT device consists of two finger-mounted probes, which include a system of inflatable latex air-cushions within a rigid external case. The probe design allows the application of a constant and evenly distributed near-diastolic counterpressure within the entire probe, which increases sensitivity by unloading arterial wall tension, and prevents venous blood pooling to avoid venoarteriolar reflex vasoconstriction. Pulsatile volume changes of the fingertip are sensed by a pressure transducer and transferred to a personal computer where the signal is band pass-filtered (0.3 to 30 Hz), amplified, displayed, and stored. | Baseline and at 1 month after placebo or L-GSH treatment | No |
| Secondary | Oxidative stress markers | Screening (V-1 - day -1): eligibility assessment; Baseline 1 (V0 - day 0): informed consent, interview, vital signs (blood pressure and heart rate), routine biochemistry (serum fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, creatinine, urea, gamma-glutamyl-transpeptidase, aspartate-amino transferase, alanine-amino transferase), specific biochemistry (total and reduced blood glutathione, plasma nitrotyrosine, plasma malondialdehyde and plasma 8-hydroxy-2'-deoxyguanosine) flow-mediated dilation (FMD) assessment, randomization and dispense drug (L-GSH or placebo - 100 mg b.i.d.); Follow-up 1 (V1 - week 4): vital signs, routine biochemistry, specific biochemistry, FMD, adverse events; Baseline 2 (V2 - week 7/8): interview, vital signs, routine biochemistry, specific biochemistry, FMD and dispense drug (L-GSH or placebo - 100 mg b.i.d.); Follow-up 2 (V3 - week 11/12): vital signs, routine biochemistry, specific biochemistry, FMD, adverse events | Baseline and at 1 month after placebo or L-GSH treatment | No |