Sublingual L-GSH Supplementation in Male Subjects With Smoking Habit and/or Hypertension
|ClinicalTrials.gov Identifier: NCT02125045|
Recruitment Status : Completed
First Posted : April 29, 2014
Last Update Posted : May 8, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Health Subjects With Cardiovascular Risk Factors||Dietary Supplement: L-GSH Dietary Supplement: Placebo||Phase 3|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|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|
|Study Start Date :||February 2014|
|Actual Primary Completion Date :||May 2014|
|Actual Study Completion Date :||May 2014|
Glutathione 100 mg tablets twice a day
Dietary Supplement: L-GSH
Reduced glutathione is formed by cysteine, glycine and glutamate. It enters into the detoxification processes of endogenous products, such as peroxides which are the final pathway of many reactions caused by cardiovascular risk factors. It also acts on the exogenous compounds, such as pollutants, heavy metals and some drugs.
Placebo Comparator: Placebo
Matching placebo will be administered for 4 weeks in a double blind fashion.
Dietary Supplement: Placebo
Placebo will be prepared using the same excipients of the dietary supplement without active substance.
- endothelium-dependent vasodilation [ Time Frame: Baseline and at 1 month after placebo or L-GSH treatment ]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.
- Oxidative stress markers [ Time Frame: Baseline and at 1 month after placebo or L-GSH treatment ]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
- Adverse events [ Time Frame: after 4, 8 and 12 weeks from the first visit V0 ]The safety will be assessed by monitoring the adverse effects related with the administration of LGSH or placebo
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02125045
|Oberdan Parodi, MD|
|Milan, Italy, 20162|
|Study Director:||Jonica Campolo, MSc||Insitute of Clinical Physiology CNR|
|Study Chair:||Gianpalolo Micheloni, MD||Niguarda Ca' Granda Hospital|