Safety of Ginkgo Biloba Leaf Extract (GiBiEx)

• ClinicalTrials.gov Identifier: NCT03004508
• Recruitment Status: Unknown
• First Posted: December 29, 2016
• Last Update Posted: December 30, 2016
• Sponsor: IRCCS San Raffaele
• Collaborator: Indena S.p.A
• Information provided by (Responsible Party): Stefano Bonassi, IRCCS San Raffaele

Study Description

Brief Summary:

Primary objective: The primary objective of this study is to assess the effect of Ginkgo biloba L. leaf extract (IDN 5933) in comparison to placebo in human subjects treated at therapeutic doses for 6 months on the level of DNA damage and genomic instability, measured with the Comet Assay and the Micronucleus assay, respectively .

Secondary objective:

The secondary objective of this study is to provide a preliminary assessment of the safety of Ginkgo biloba L. leaf extract (IDN 5933) in human subjects treated at therapeutic doses in term of adverse drug reaction, hepatotoxicity, genotoxicity.

Condition or disease	Intervention/treatment	Phase
Healthy	Dietary Supplement: Gingko Biloba Extract; Dietary Supplement: Placebo	Phase 2

Detailed Description:

The study will be a randomised clinical trial comparing subjects receiving twice-daily doses of either 120-mg of Ginkgo biloba L. leaf extract (IDN 5933) or placebo for a 6 months period.

Primary Endpoints:

• DNA Damage assessed with the Comet assay as proportion of DNA in the tail.
• Micronucleus frequency (MN) in peripheral blood lymphocytes (Frequency per 1000 binucleated cells).

Secondary Endpoints:

• Complete clinical assessment at the beginning and at the end of the study.
• Occurrence of Adverse drug reactions in individuals treated with GBE or placebo.
• Liver functions will be monitored according to biological laboratory examinations and clinical symptoms. A subgroup of individuals will be monitored also for genetic parameters concerning expression patterns of genes putatively associated to early events of HCC carcinogenesis Clinical and biological parameters will be measured in the study groups at the beginning (T0) and at the end of the study (T2).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Antioxidant Effect of Treatment With Ginkgo Biloba L. Leaf Extract (IDN 5933) on DNA Cell Maintenance and Genomic Stability: A Randomised Study Versus Placebo
• Study Start Date: July 2015
• Estimated Primary Completion Date: December 2016
• Estimated Study Completion Date: January 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Gingko biloba Extract	Dietary Supplement: Gingko Biloba Extract; 120mg/day, twice a day, 6 month; Other Name: IDN 5933
Placebo Comparator: Placebo	Dietary Supplement: Placebo; 120mg/day, twice a day, 6 month

Outcome Measures

Primary Outcome Measures :

1. DNA Damage [ Time Frame: through study completion, an average of 1 year ]
   DNA Damage assessed with the Comet assay as proportion of DNA in the tail
2. Micronucleus frequency [ Time Frame: through study completion, an average of 1 year ]
   Micronucleus frequency (MN) in peripheral blood lymphocytes (Frequency per 1000 binucleated cells)

Secondary Outcome Measures :

1. Clinical assessment [ Time Frame: through study completion, an average of 1 year ]
   Complete clinical assessment at the beginning and at the end of the study by physiological parameters
2. Liver functions [ Time Frame: through study completion, an average of 1 year ]
   Liver functions will be monitored according to biological laboratory examinations and clinical symptoms
3. Gene Expression [ Time Frame: A subgroup of individuals will be monitored also through study completion, an average of 1 year ]
   Expression patterns of genes putatively associated to early events of HCC carcinogenesis
4. Adverse drug reactions [ Time Frame: through study completion, an average of 1 year ]
   Occurrence of Adverse drug reactions in individuals treated with GBE or placebo

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male and female senior, residents of nursing homes, with no known clinically significant pathology as assessed by the investigator
• Life expectancy of greater than 1 year
• Subjects must have given written informed consent in accordance with ICH-GCP (International Conference on Harmonization - Good Clinical Practice) and local laws and regulations

To perform the experiment in a typical population treated with Ginkgo biloba L. leaf extract ( IDN 5933) the study will be performed among the residents of nursing homes among the structures of the San Raffaele network, i.e., The San Raffaele Montecompatri, the San Raffaele Rocca di Papa and the San Raffaele Sabaudia . The use of institutionalised subjects will allow a good compliance to the treatment, which will be administered by the nursing homes nurses.

Subjects meeting inclusion criteria and signing the informed consent will be randomised to receive 120-mg/twice per day of Ginkgo biloba L. leaf extract ( IDN 5933) or placebo.

Exclusion Criteria:

• Life expectancy of less than 1 year
• Treatment with anticoagulant and antiplatelet drugs in subjects with previous report of increased bleeding tendency
• Cognitive impairment
• Refuse to sign the informed consent

Contacts and Locations

Locations

Italy

IRCCS San Raffaele Pisana

Rome, Italy, 00166

Sponsors and Collaborators

IRCCS San Raffaele

Indena S.p.A

Investigators

• Principal Investigator: Stefano Bonassi, PhD; IRCCS San Raffaele

More Information

Publications of Results:

National Toxicology Program. Toxicology and carcinogenesis studies of Ginkgo biloba extract (CAS No. 90045-36-6) in F344/N rats and B6C3F1/N mice (Gavage studies). Natl Toxicol Program Tech Rep Ser. 2013 Mar;(578):1-183.

Russo P, Frustaci A, Del Bufalo A, Fini M, Cesario A. Multitarget drugs of plants origin acting on Alzheimer's disease. Curr Med Chem. 2013;20(13):1686-93. doi: 10.2174/0929867311320130008.

Heinonen T, Gaus W. Cross matching observations on toxicological and clinical data for the assessment of tolerability and safety of Ginkgo biloba leaf extract. Toxicology. 2015 Jan 2;327:95-115. doi: 10.1016/j.tox.2014.10.013. Epub 2014 Nov 11.

Luo Y, Smith JV, Paramasivam V, Burdick A, Curry KJ, Buford JP, Khan I, Netzer WJ, Xu H, Butko P. Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12197-202. doi: 10.1073/pnas.182425199. Epub 2002 Sep 4.

Bonassi S, Znaor A, Ceppi M, Lando C, Chang WP, Holland N, Kirsch-Volders M, Zeiger E, Ban S, Barale R, Bigatti MP, Bolognesi C, Cebulska-Wasilewska A, Fabianova E, Fucic A, Hagmar L, Joksic G, Martelli A, Migliore L, Mirkova E, Scarfi MR, Zijno A, Norppa H, Fenech M. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis. 2007 Mar;28(3):625-31. doi: 10.1093/carcin/bgl177. Epub 2006 Sep 14.

Collins A, Koppen G, Valdiglesias V, Dusinska M, Kruszewski M, Moller P, Rojas E, Dhawan A, Benzie I, Coskun E, Moretti M, Speit G, Bonassi S; ComNet project. The comet assay as a tool for human biomonitoring studies: the ComNet project. Mutat Res Rev Mutat Res. 2014 Jan-Mar;759:27-39. doi: 10.1016/j.mrrev.2013.10.001. Epub 2013 Oct 31.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bonassi S, Prinzi G, Lamonaca P, Russo P, Paximadas I, Rasoni G, Rossi R, Ruggi M, Malandrino S, Sanchez-Flores M, Valdiglesias V, Benassi B, Pacchierotti F, Villani P, Panatta M, Cordelli E. Clinical and genomic safety of treatment with Ginkgo biloba L. leaf extract (IDN 5933/Ginkgoselect(R)Plus) in elderly: a randomised placebo-controlled clinical trial [GiBiEx]. BMC Complement Altern Med. 2018 Jan 22;18(1):22. doi: 10.1186/s12906-018-2080-5.

• Responsible Party: Stefano Bonassi, Head, Clinical and Molecular Epidemiology, IRCCS San Raffaele
• ClinicalTrials.gov Identifier: NCT03004508
• Other Study ID Numbers: IDN5933
• First Posted: December 29, 2016
• Last Update Posted: December 30, 2016
• Last Verified: December 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Stefano Bonassi, IRCCS San Raffaele:

Ginkgo Biloba Extract; Safety; Genomic Stability; DNA cell maintenance

Additional relevant MeSH terms:

Genomic Instability; Pathologic Processes