Efficacy and Safety Study of a IMSS Developed Phytopharmaceutical for the Treatment of Anxiety.

NCT03702803 | Unknown Phase 2 DMC

• 1 other identifier: Galphimia glauca phytopharm
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief Summary

The investigator's group at the Mexican Institute of Social Security has worked for more than 20 years in the scientific research of the plant species Galphimia glauca Cav., which is used in Mexican Traditional Medicine for the treatment of mental disorders. With the obtained results it was possible the development of a phytopharmaceutical elaborated with the extract of this plant, which was standardized in its content of Galphimine-B (G-B). This new compound is a nor, seco-triterpene, which possesses selective effects on the central nervous system. Through electrophysiological neuronal unitary records it was identified that G-B acts on the ventral tegmental area (VTA), and exerts its effect on (N-methyl-D-aspartate) NMDA receptors in dopaminergic neurons. The new phytopharmaceutical, elaborated from a standardized extract (in its G-B content) of G. glauca, was subjected to a double blind and randomized clinical study that compared its efficacy and therapeutic tolerability with a similar drug formulated with lorazepam in patients with diagnosis of generalized anxiety disorder (GAD). In a total of 152 patients, it was evidenced that the phytomedicine administered orally (for 4 weeks) was able to significantly reduce anxiety, in a similar way as lorazepam did, but with better tolerability. Several patients who were treated with lorazepam had to leave the study because they had daytime sleepiness. In clinical practice, different benzodiazepines have specific indications. In the case of anxiety disorders, the drug of first choice is Alprazolam, this, because it manifests a more powerful anxiolytic effect with a lower degree of sedation and daytime sleepiness. Objective: The present project aims to compare the efficacy and therapeutic safety of an elaborated phytopharmaceutical with the standardized extract of Galphimia glauca with Alprazolam .

Conditions

Generalized Anxiety Disorder

Keywords

Phytopharmaceutical; Anxiety; Outpatients

Outcome Measures

Primary Outcomes (1)

• Therapeutic efficacy: improvement of the clinical condition higher than 90%. It will be measured by means of the Hamilton Rating Scale for Anxiety.

  It will be considered when the patient presents an improvement of the clinical condition higher than 90% on the scales of measurement (HAM-A). Hamilton Rating Scale for Anxiety (HAM-A) consisted of 14 items that assessed the severity of anxiety. Each item was scored using a 5-point scale (0=not present to 4=very severe). The HAM-A Total Score could have ranged from 0 to 56 and higher scores indicated a greater degree of symptom severity. Scores 14-21 indicate mild anxiety; scores 21-29 indicate moderate anxiety; scores over 29 indicate severe anxiety

  Up to 10 weeks

Secondary Outcomes (2)

• Therapeutic Tolerability: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Up to 10 weeks

• Clinical Global Impression of Improvement Scale (CGI-I). A 7 points scale that is used to evaluate how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention.

  Up to 10 weeks

Study Arms (2)

Galphimia glauca standardized extract

EXPERIMENTAL

Patients with a clinical diagnosis of GAD (with a score of 18 points or more on the Hamilton anxiety scale) that will be included in the experimental group and will be assigned the treatment consisting of hard gelatin capsules with a pharmaceutical formulation prepared with a standardized extract from G. glauca, which will be administered once a day.

Dietary Supplement: Galphimia glauca standardized extract

alprazolam 1mg

ACTIVE COMPARATOR

Patients with a clinical diagnosis of GAD (with a score of 18 points or more on the Hamilton anxiety scale) that will be included in the control group and will be assigned the treatment consisting of hard gelatin capsules with the drug Alprazolam (1 mg ), which will be administered once a day.

Drug: alprazolam 1mg

Interventions

Galphimia glauca standardized extract DIETARY_SUPPLEMENT

Each patient will be administered with a capsule once a day (in the morning), for 10 weeks. A capsule contains the standardized extract of Galphimia glauca corresponding to 0.374 mg of Galphimine-B

Galphimia glauca standardized extract

alprazolam 1mg DRUG

Each patient will be administered once a day (in the morning) for 10 weeks. A capsule contains 1 mg Alprazolam

Also known as: Alprazolam

alprazolam 1mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of both sexes
• Eighteen years of age and older
• Clinical diagnosis of Generalized Anxiety Disorder
• Eighteen points or more on Hamilton Anxiety Scale
• Without previous treatment for this disease (for at least one month before).
• In case of being women of reproductive age, who are not pregnant or lactating.
• To sign an informed consent letter of participation in the investigation.

You may not qualify if:

• Patients who have treatment for their condition
• Patients who have another mental disorder added
• Patients with alcoholism, smoking or drug addiction
• Patients who live alone
• Ingest of drugs for insomnia
• Ingest of drugs of the Monoamine Oxidase Inhibitors group
• Patients with epilepsy
• Patients who operate dangerous machinery
• Patients who have to drive at work (car, truck or other motor vehicle) for a long time.

Sponsors & Collaborators

• Coordinación de Investigación en Salud, Mexico: lead

Study Sites (1)

Regional General Hospital Number 1 at Cuernavaca, Morelos. Mexican Insitute of Social Security

Cuernavaca, Morelos, Mexico

RECRUITING

Related Publications (20)

• Tortoriello J, Lozoya X. Effect of Galphimia glauca methanolic extract on neuropharmacological tests. Planta Med. 1992 Jun;58(3):234-6. doi: 10.1055/s-2006-961442.

  PMID: 1409977 RESULT

• Tortoriello J, Ortega A. Sedative effect of galphimine B, a nor-seco-triterpenoid from Galphimia glauca. Planta Med. 1993 Oct;59(5):398-400. doi: 10.1055/s-2006-959717.

  PMID: 8255929 RESULT

• Tortoriello J, Ortega A, Herrera-Ruiz M, Trujillo J, Reyes-Vazquez C. Galphimine-B modifies electrical activity of ventral tegmental area neurons in rats. Planta Med. 1998 May;64(4):309-13. doi: 10.1055/s-2006-957440.

  PMID: 9619110 RESULT

• Osuna L, Pereda-Miranda R, Tortoriello J, Villarreal ML. Production of the sedative triterpene galphimine B in Galphimia glauca tissue culture. Planta Med. 1999 Mar;65(2):149-52. doi: 10.1055/s-1999-14057.

  PMID: 10193207 RESULT

• Prieto-Gomez B, Tortoriello J, Vazquez-Alvarez A, Reyes-Vazquez C. Galphimine B modulates synaptic transmission on dopaminergic ventral tegmental area neurons. Planta Med. 2003 Jan;69(1):38-43. doi: 10.1055/s-2003-37043.

  PMID: 12567277 RESULT

• Gonzalez-Cortazar M, Tortoriello J, Alvarez L. Norsecofriedelanes as spasmolytics, advances of structure-activity relationships. Planta Med. 2005 Aug;71(8):711-6. doi: 10.1055/s-2005-871224.

  PMID: 16142633 RESULT

• Rojas G, Aranda E, Navarro V, Zamilpa A, Tortoriello J. In vitro propagation of Galphimia glauca and content of the sedative compound galphimine-B in wild and micropropagated plants. Planta Med. 2005 Nov;71(11):1076-8. doi: 10.1055/s-2005-873136.

  PMID: 16320215 RESULT

• Herrera-Ruiz M, Jimenez-Ferrer JE, De Lima TC, Aviles-Montes D, Perez-Garcia D, Gonzalez-Cortazar M, Tortoriello J. Anxiolytic and antidepressant-like activity of a standardized extract from Galphimia glauca. Phytomedicine. 2006 Jan;13(1-2):23-8. doi: 10.1016/j.phymed.2005.03.003. Epub 2005 Jun 28.

  PMID: 16360929 RESULT

• Herrera-Ruiz M, Gonzalez-Cortazar M, Jimenez-Ferrer E, Zamilpa A, Alvarez L, Ramirez G, Tortoriello J. Anxiolytic effect of natural galphimines from Galphimia glauca and their chemical derivatives. J Nat Prod. 2006 Jan;69(1):59-61. doi: 10.1021/np050305x.

  PMID: 16441069 RESULT

• Mangas S, Bonfill M, Osuna L, Moyano E, Tortoriello J, Cusido RM, Pinol MT, Palazon J. The effect of methyl jasmonate on triterpene and sterol metabolisms of Centella asiatica, Ruscus aculeatus and Galphimia glauca cultured plants. Phytochemistry. 2006 Sep;67(18):2041-9. doi: 10.1016/j.phytochem.2006.06.025. Epub 2006 Jul 28.

  PMID: 16876832 RESULT

• Aguilar-Santamaria L, Ramirez G, Herrera-Arellano A, Zamilpa A, Jimenez JE, Alonso-Cortes D, Cortes-Gutierrez EI, Ledesma N, Tortoriello J. Toxicological and cytotoxic evaluation of standardized extracts of Galphimia glauca. J Ethnopharmacol. 2007 Jan 3;109(1):35-40. doi: 10.1016/j.jep.2006.06.013. Epub 2006 Jul 8.

  PMID: 16930894 RESULT

• Herrera-Arellano A, Jimenez-Ferrer E, Zamilpa A, Morales-Valdez M, Garcia-Valencia CE, Tortoriello J. Efficacy and tolerability of a standardized herbal product from Galphimia glauca on generalized anxiety disorder. A randomized, double-blind clinical trial controlled with lorazepam. Planta Med. 2007 Jul;73(8):713-7. doi: 10.1055/s-2007-981539. Epub 2007 Jun 11.

  PMID: 17562493 RESULT

• Osuna L, Moyano E, Mangas S, Bonfill M, Cusido RM, Pinol MT, Zamilpa A, Tortoriello J, Palazon J. Immobilization of Galphimia glauca plant cell suspensions for the production of enhanced amounts of Galphimine-B. Planta Med. 2008 Jan;74(1):94-9. doi: 10.1055/s-2007-993763. Epub 2008 Jan 4.

  PMID: 18176908 RESULT

• Jimenez-Ferrer E, Herrera-Ruiz M, Ramirez-Garcia R, Herrera-Arellano A, Tortoriello J. Interaction of the natural anxiolytic Galphimine-B with serotonergic drugs on dorsal hippocampus in rats. J Ethnopharmacol. 2011 Sep 1;137(1):724-9. doi: 10.1016/j.jep.2011.06.029. Epub 2011 Jul 1.

  PMID: 21742023 RESULT

• Herrera-Arellano A, Jimenez-Ferrer JE, Zamilpa A, Garcia-Alonso G, Herrera-Alvarez S, Tortoriello J. Therapeutic effectiveness of Galphimia glauca vs. lorazepam in generalized anxiety disorder. A controlled 15-week clinical trial. Planta Med. 2012 Sep;78(14):1529-35. doi: 10.1055/s-0032-1315110. Epub 2012 Jul 24.

  PMID: 22828921 RESULT

• Gonzalez-Cortazar M, Herrera-Ruiz M, Zamilpa A, Jimenez-Ferrer E, Marquina S, Alvarez L, Tortoriello J. Anti-inflammatory activity and chemical profile of Galphimia glauca. Planta Med. 2014 Jan;80(1):90-6. doi: 10.1055/s-0033-1360150. Epub 2013 Dec 11.

  PMID: 24338551 RESULT

• Abarca Vargas R, Zamilpa A, Aguilar FA, Herrera-Ruiz M, Tortoriello J, Jimenez-Ferrer E. Pharmacokinetic study in mice of galphimine-A, an anxiolytic compound from Galphimia glauca. Molecules. 2014 Mar 12;19(3):3120-34. doi: 10.3390/molecules19033120.

  PMID: 24625685 RESULT

• Jimenez-Ferrer E, Santillan-Urquiza MA, Alegria-Herrera E, Zamilpa A, Nogueron-Merino C, Tortoriello J, Navarro-Garcia V, Aviles-Flores M, Fuentes-Mata M, Herrera-Ruiz M. Anxiolytic effect of fatty acids and terpenes fraction from Aloysia triphylla: Serotoninergic, GABAergic and glutamatergic implications. Biomed Pharmacother. 2017 Dec;96:320-327. doi: 10.1016/j.biopha.2017.10.024. Epub 2017 Oct 7.

  PMID: 29017144 RESULT

• Santillan-Urquiza MA, Herrera-Ruiz M, Zamilpa A, Jimenez-Ferrer E, Roman-Ramos R, Tortoriello J. Pharmacological interaction of Galphimia glauca extract and natural galphimines with Ketamine and Haloperidol on different behavioral tests. Biomed Pharmacother. 2018 Jul;103:879-888. doi: 10.1016/j.biopha.2018.04.082. Epub 2018 Apr 24.

  PMID: 29710504 RESULT

• Romero-Cerecero O, Islas-Garduno AL, Zamilpa A, Herrera-Arellano A, Jimenez-Ferrer E, Tortoriello J. Galphimine-B Standardized Extract versus Alprazolam in Patients with Generalized Anxiety Disorder: A Ten-Week, Double-Blind, Randomized Clinical Trial. Biomed Res Int. 2019 Jan 30;2019:1037036. doi: 10.1155/2019/1037036. eCollection 2019.

  PMID: 30834253 DERIVED

MeSH Terms

Conditions

Generalized Anxiety Disorder; Anxiety Disorders

Interventions

Alprazolam

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• JAIME TORTORIELLO, Dr

  Centro de Investigación Biomédica del Sur (CIBIS), IMSS

  PRINCIPAL INVESTIGATOR

• SUSANA NAVARRETE, DR

  CIS MEXICO

  STUDY CHAIR

Central Study Contacts

JAIME TORTORIELLO, Dr.

CONTACT

+527773612155; jtortora2@yahoo.es

OFELIA ROMERO-CERECERO, Dr

CONTACT

+527773612194; orcerecero@yahoo.com.mx

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Both treatments have an identical appearance and are packed in hard gelatin capsules, which are packed in individual aluminum and PVC blisters with 10 doses each. Three blisters with ten doses are introduced in cardboard boxes and identified through a folio number.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Southern Biomedical Research Center

Model Details: Participants will be randomly assigned to one of the two groups: the experimental group receiving a phytopharmaceutical elaborated with the standardized extract from G. glauca, and a control group receiving an identical formulation containing Alprazolam

Study Record Dates

• First Submitted: October 1, 2018
• First Posted: October 11, 2018
• Study Start: March 16, 2016
• Primary Completion: September 19, 2020
• Study Completion: October 19, 2020
• Last Updated: July 14, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)