Generalized Anxiety Disorder Clinical Trial
Official title:
Efficacy and Safety Study of a IMSS Developed Phytopharmaceutical for the Treatment of Anxiety. Double Blind and Randomized Clinical Trial Controlled With Alprazolam
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 .
A double-blind, randomized, controlled clinical study will be conducted in patients with GAD.
The development of the phytopharmaceutical will be carried out at the Southern Biomedical
Research Center, belonging to the Mexican Institute of Social Security. The preparation of
the plant material, extraction, concentration, standardization of the vegetable drug, the
design and production of the experimental drug as well as the control treatment will be
carried out in this site.
The clinical trial will be developed with outpatient from the Primary Care Family Medicine
Unit of the Regional General Hospital No. 1 of the Mexican Institute of Social Security in
Cuernavaca, Morelos, Mexico.
SUBJECTS. Patients of both sexes aged 18 years and older who present Generalized Anxiety
disorder (GAD) and who meet the selection criteria.
Experimental group 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 (in its content of Galphimine-B, G-B) of G.
glauca, which will be administered once a day.
Control group 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.
GENERAL DESCRIPTION OF THE STUDY The project will be promoted through posters that will be
placed in strategic areas of the Medical Unit. In addition, brochures will be distributed
with information about anxiety and the requirements to enter the project. There will also be
support staff, Who will be in charge of giving conferences related with GAD in the waiting
Hospital rooms. Once a person is identified who is a candidate to be included in the study,
an invitation will be made to go to the clinical research office for evaluation.
In the research office, a trained physician, will practice the candidates a medical history
and physical examination. The above, with the purpose of corroborating the diagnosis of GAD
through the application of the Hamilton Anxiety Scale. This fully validated instrument will
serve to make the clinical diagnosis of the condition.
If the questionnaire applied to the candidate gives us a total score of 18 points or more,
the patient will be considered a candidate to enter the study. In order to be admitted, the
patient, in addition must to have a clinical diagnosis of GAD, must meet the selection
criteria established in this study. Once the patient complies with these two aspects will be
given the necessary information about the study and about their participation in it. Patient
must also sign a letter of informed consent, this letter will contain information about the
characteristics of the study, benefits to the population, commitment that the patient
acquires when participating, commitments that the researcher acquires when the patient is
included and the rights that the participant acquires.
Each of the participants will be randomly assigned the corresponding medication (which can be
experimental or control) through a procedure based on a table of random numbers. The dosage
of medications will be every 24 hours, administered orally in the morning. The indication
will be given that the medication is taken together with the food. The duration of the
administration of the medication will be for ten weeks.
In addition, each of the patients will be provided oral and written instructions on the form
and times to take the medication, as well as the possible adverse effects and
hygienic-dietetic measures that must be taken.
The patient will be following weekly, but may go to receive care at the time you require it.
At each appointment, the state of health and the evolution of the condition will be
evaluated, and the overall improvement scale will also be applied. At each appointment,
patient will be given a control card (to each patient) where he will write down the days the
medication was taken and whether or not there were any adverse effects during that
administration period. In this way, adherence to treatment and tolerability will be
evaluated.
The values of the Hamilton anxiety scale and the global improvement scale will be used to
define the effectiveness, the therapeutic success or failure.
The final assessment of efficacy, tolerability, attachment and therapeutic success will be
made during the last appointment. A summary will be sent to the family doctor of each of the
participants and their discharge from the study.
SAMPLE SIZE The size of the sample was calculated according to the formula for comparison of
two proportions, taking as background the efficacy that the species showed in previous
clinical studies on generalized anxiety. The procedure yielded a total of 105 patients. 15%
will be added to the sample size to compensate for possible losses, which leaves us with a
final sample size of 122 patients.
DATA ANALYSIS. The results will be analyzed through descriptive statistics with frequencies
and percentages. The X2 test will be used for the analysis of differences in proportions and
ANOVA for mean differences, as well as Tukey's test for the difference between groups. Values
of p less than 0.05 will be used to define differences between statistically significant
groups
ETHICAL ASPECTS Project research was evaluated and approved by the National Scientific
National Committee.
The species G. glauca has been used for many years in traditional Mexican medicine to treat
some mental disorders. A pharmaceutical formulation, elaborated with the extract obtained
from G. Glauca has been used in clinical projects to evaluate its efficacy and tolerability
in patients with anxiety disorder. The administration time has been four weeks with a daily
dose of a standardized product in 0.374 mg of G-B per dose. No significant adverse effects
have been identified. Because it is a phytopharmaceutical that has shown good tolerability,
the risk of adverse effects is low.
In developing this project, the aim is to have a novel alterative treatment that expresses a
different mechanism of action, and that shows efficacy and tolerability in the treatment of
GAD, but also that the effect obtained is comparable or better than that of a drug,
elaborated with Alprazolam, which is the benzodiazepine of first choice and with specific
indication for the treatment of this condition.
According to the Regulation of the General Law of Health in Research, there is no risk in the
patients who will participate in the present project. The project will only include adults;
will not include women with pregnancy or lactation or another sector vulnerable to research.
The research procedures are in accordance with the ethical rules of investigation, the
Regulation of the General Law of Health in the field of health research and the Declaration
of Helsinki and its amendments. All information obtained by conducting this study will be
handled in a scientific and confidential manner. The clinical files will be kept under guard
and the management of the information for the analysis of results will be done exclusively
with the assigned folio number. No patient will be included if it is not widely known in
which it will consist of their participation, the background of the medication, time that
will last the study, dose that will be administered and frequency of the same, laboratory
studies to which you will be subjected in addition to informing you that you have the freedom
to withdraw from the study at the time you want. The patient will receive extensive and clear
information about the protocol, the content of the letter of informed consent will be read,
will be given space for the formulation of questions or concerns.
ASPECTS OF SECURITY The patients included in the study will be evaluated clinically in each
of the appointments. In addition, at the beginning of the study and at the end of the
administration period, laboratory tests will be performed to assess liver and kidney
function. Medical surveillance with the search for adverse events will be included in each of
the visits. In case of identifying any adverse effect, it will be monitored until its
disappearance and the measures described below will be applied according to the event's
rating.
An adverse event will be considered as any unpleasant, unintentional harmful medical
occurrence that a patient submits to the administration of a pharmaceutical product, which
may or may not have a causal relationship to the treatment.
The intensity of the adverse events refers to the maximum intensity with which the patient
and / or the investigator qualify the adverse events that the patient presents.
1. Mild: The adverse effect is presented, but it is easily tolerated and does not require
treatment
2. Moderate: the adverse effect is enough to interfere with normal activities
3. Severe: The adverse effect incapacitates the subject
4. Serious: Any adverse effect that results in the death of the patient, endangers life,
requires hospitalization, causes disability or persistent or significant disability,
causes a congenital anomaly or cancer, requiring surgical intervention to prevent
permanent sequel or develop drug dependence or abuse Overdose is defined as the exposure
without a specific therapeutic goal to an amount of medication of at least twice the
maximum daily dose reported in the study protocol.
In all cases in which a severe adverse effect is identified, the treatment will be suspended
and the patient will be removed from the study. In addition to the above, the patient will be
referred for care in the specialized medical area and will be monitored until the resolution
of the adverse effect. In the event of a serious adverse effect, the treatment will be
suspended, the patient will be removed from the study and the blind code of the patient will
be opened. In those cases in which there is a mild or moderate adverse effect, it will be
reported in the patient's clinical file, it will be attended immediately and surveillance
will be maintained until its complete remission. In these cases, the treatment will not be
suspended, and the patient will remain within the investigation.
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