Sublingual L-GSH Supplementation in Male Subjects With Smoking Habit and/or Hypertension

NCT02125045 | Completed Phase 3

• 1 other identifier: 215_062013
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Health Subjects With Cardiovascular Risk Factors

Keywords

GSH; cardiovascular risk factors; endothelial dysfunction; oxidative stress

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Oxidative stress markers

  Baseline and at 1 month after placebo or L-GSH treatment

Other Outcomes (1)

• Adverse events

  after 4, 8 and 12 weeks from the first visit V0

Study Arms (2)

L-GSH

EXPERIMENTAL

Glutathione 100 mg tablets twice a day

Dietary Supplement: L-GSH

Placebo

PLACEBO COMPARATOR

Matching placebo will be administered for 4 weeks in a double blind fashion.

Dietary Supplement: Placebo

Interventions

L-GSH DIETARY_SUPPLEMENT

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.

L-GSH

Placebo DIETARY_SUPPLEMENT

Placebo will be prepared using the same excipients of the dietary supplement without active substance.

Placebo

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Niguarda Hospital: lead

Study Sites (1)

Oberdan Parodi, MD

Milan, Milan, 20162, Italy

Location

Study Officials

• Jonica Campolo, MSc

  Insitute of Clinical Physiology CNR

  STUDY DIRECTOR

• Gianpalolo Micheloni, MD

  Niguarda Ca' Granda Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2013
• First Posted: April 29, 2014
• Study Start: February 1, 2014
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: May 8, 2014

Record last verified: 2014-05

Locations

IT (1)