Double Blind Evaluation of Gamma-aminobutyric Acid Tartarate 100 mg, Glutamic Acid 100 mg, Dibasic Calcium Phosphate 50 mg, Thiamine Nitrate 25 mg, Pyridoxine Chloride 10 mg and Cyanocobalamin 5 mcg Versus Ginger for Vertigo-kinetosis
Phase: PHASE4
Conditions: Vertigo
Sponsor: Fundação Educacional Serra dos Órgãos

 
 
 
 
 
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Study Title 
 
Double Blind Clinical Evaluation on the combination of 
Gamma-Aminobutyric Acid Tartrate 100mg, Glutamic 
Acid 100mg, Dibasic Calcium Phosphate 50mg, Thiamine 
Nitrate 25mg, Pyridoxine Hydrochloride 10mg and 
Cyanocobalamin 5mcg compared to Ginger Extract as 
adjuvant therapy in symptomatic control of chronic 
vertigo motion sickness 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
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1. BACKGROUND:  
Motion sickness is a chronic condition characterized by vestibular changes in response to stimuli 
caused either by movement or movement perception triggered by car, train, ship or aircraft 
transportation, amusement park rides, virtual reality and simulators, walking, exercising, as well as 
under the absence of gravity in space. It can also be triggered by movies and television shows that 
exhibit  glowing colors, movement, and focus shifting. 
The studied combination drug is composed, among other substances, by GABA (gamma-
aminobutyric acid), the main inhibitory neurotransmitter of the central nervous system. The former 
lowers anxiety symptoms. Its precursor, glutamic acid, is the amino acid found in greater concentration 
under free form in the CNS; it is closely related to brain metabolism and, in contrast to GABA, it is the 
main excitatory neurotransmitter; glutamic acid also has anesthetic and anxyolytic therapeutic 
properties. Thiamine or vitamin B1 is a cofactor in the synthesis of acetylcholine, which plays a central 
role in the initiation and propagation of neural impulse in the CNS as well as it does in the skeletal and 
myocardial muscles. Pyridoxine or vitamin B6 plays a role in the synthesis of neurotransmitters such 
as dopamine as well as in the metabolism of tryptophan, resulting in an increase in serotonin so 
providing well-being and anxiety relief. Pyridoxine is essential for the proper functioning of the CNS 
(including at nausea and vomiting center) and immune system. Cyancobalamin or Vitamin B12 plays 
a role in the formation of red blood cells, in the growth and repair of nerve fibers as well as in pain 
relief. Importantly it also improves blood flow in the brain, with secondary vertigo improvement 
(Goodman & Gilman's, 2018; Gomes, Coutinho, Geller 2018). The combined use of these substances 
provides relief of  vertigo due to motion sickness. Zingiber officinale is a species of the Zingiberacaea 
family, widely used in traditional and herbal medicine for the treatment of various clinical conditions 
such as vertigo. 
Keywords: Kinetosis, Gamma-aminobutyric acid tartrate, glutamic acid, calcium phosphate dibasic, 
thiamine nitrate, pyridoxine hydrochloride, cyanocobalamin, Zingiber officinale, Motion Sickness 
Assessment Questionnaire 
2. HYPOTHESIS:  
Oral administration of the combination gamma-aminobutyric acid tartrate 100mg, glutamic acid 
100mg, dibasic calcium phosphate 50mg, thiamine nitrate 25mg, pyridoxine hydrochloride 10mg and 
cyanocobalamin 5mcg or Zingiber officinale 160mg (8mg Gingerols) results in symptomatic 
improvement of vertigo due to motion sickness, according to pre- and post-treatment MSAQ 
statements. 
3. OBJECTIVES: 
3.1 Primary objective: To evaluate the efficacy and safety of the combination gamma-aminobutyric 
acid tartrate 100mg, glutamic acid 100mg, dibasic calcium phosphate 50mg, thiamine nitrate 25mg, 
pyridoxine hydrochloride 10mg and cyanocobalamin 5mcg versus Zingiber officinale 160mg dry extract 
(8mg gingerols) as adjuvant therapy in symptomatic control of chronic vertigo motion sickness. 
3.2 Secondary objective: To assess pre- and post-therapeutic efficacy according to MSAQ scores and 
sub-scores, as well as tolerability of the association. 
4. STUDY LOCATION: UNIFESO. 

 
 
 
 
 
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5. PROPOSED METHODOLOGY: 
5.1 Study design and population:  
Patients sample for this study was calculated using the Power & Precision software version 4.0, based 
on the null hypothesis that the proportion of patients who might show clinical improvement would be 
identical in both groups. Approximately 334 patients are expected to be included, with 167 receiving 
the combination and 167 receiving Z. officinale dry extract. The level for statistical significance (alpha) 
was set at 0.050, and the test is two-tailed. With a sample size of 167 patients per group, the study has 
a power of 36.4% to generate a statistically significant result, with a proportional difference between 
groups estimated as 0.05. This will be a double-blind randomized study in patients with chronic vertigo-
motion sickness. The treatment will have a total duration of 7 days. 
After undersigning the Informed Consent Form, participants will be evaluated for inclusion and non-
inclusion criteria. It is estimated that 451 recruited participants will be necessary to reach 334 
evaluable participants. A sequential number from 001 will be assigned to each participant included in 
the study, in order to preserve patients' identity. 
INCLUSION CRITERIA 
To qualify for inclusion in this study, the 
participant must meet all of the criteria listed 
below: 
• Participant of both sexes aged between 18 
and 65 years 
• Clinical presentation of motion sickness 
• Female participant of reproductive age 
agrees to use contraception during the study 
period 
• Participant read, understood, undersigned 
and dated the free and informed consent 
form 
NON-INCLUSION CRITERIA 
Participants will be excluded from the study if 
they present: 
• Hypersensitivity to any component of the 
study drug 
• Gallstone history 
• History of gastric irritation (according to 
product package insert) 
• Arterial blood pressure >145/100mmHg 
(according to product package insert) 
• Concomitant use of other medications for 
the treatment of motion sickness 
Four assessments will be carried out for vertigo - MSAQ (motion sickness assessment 
questionnaire), consisting of a pre-treatment assessment and three assessments during 
treatment, for both study groups. The primary variable in this study will be the MSAQ answered 
by the study subjects. The MSAQ consists of 16 questions, answered on a scale from one to nine 
points, which assesses the gastrointestinal, central and peripheral nervous system and soporous 
symptoms related to motion sickness. Secondary variables include the Investigating Physician's 
Assessment (10-point scale), willingness to continue treatment, physical examination results 
and vital signs collected during face-to-face visits to the study center, and the occurrence, 
duration, and severity of any adverse events which might have occurred during the treatment 
period. 
The Clinical Research Form will be filled out, stored, coded, and the data will be analyzed 
using the GraphPad Prism program, version 5.0. Frequency tables will be generated, central 
tendency measurements will be taken (mean, median, mode) and the percentages will be 

 
 
 
 
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calculated using the number of analyzed values as the denominator. Whenever relevant, 
confidence intervals of proportions will be calculated. 
4. Study Procedures 
4.1. Visit 1 / Pre-Treatment: will be held at the study center. After informed consent signature 
and inclusion and non-inclusion criteria assessment, an evaluation will be carried out covering: 
• Date of birth, gender, ethnicity, medical history, history of motion sickness, acute and 
chronic illnesses, concomitant medications 
• Physical examination [height (cm), weight (kg), BMI (kg/cm2), arterial blood pressure 
(mmHg), heart rate (bpm), respiratory rate (ipm)] 
• Global Evaluation of the Investigating Physician (10-point graduated scale) 
• Routine laboratory tests 
• Imaging exams (MRI, CT, EEG) at attending physician's discretion. 
 
4.2 Study Medicine and MSAQ  
During Visit 1, participants will be given  the  study medicine to be used during the treatment 
period. Each  participant will receive a total of 5 tablets - three tablets for the expected 
evaluations, and two extra tablets in case the former are lost. MSAQ will be fulfilled before and 
after treatment. Then participants will receive the printed Four-Way MSAQ. The former  will be 
asked to fulfill MSAQ at four different times (Travel 1, Travel  2, Travel  3  and Travel 4). 
The first MSAQ form will be fulfilled after a ride of at least 15 minutes, with no use of the study 
drug (Travel 1). Before Travels  2, 3, and  4, the participant will be instructed to take one tablet 
30 minutes before them and to answer the questionnaire at its end. In addition to MSAQ other 
data are: travel date and duration (standard end time), type of transport (ferry, train, subway, 
car, bus), and time  of completion of the questionnaire. 
4.3 Visit 2 / Post-Treatment: it will occur either at the end of the treatment period or if the 
study participant  is withdrawn. During this visit, participants will return to the study center, 
where the study material (study medicine and MSAQ) will be collected and the following 
procedures performed: 
• 
Physical examination [weight (kg), BMI (kg/cm2), blood pressure (mmHg), heart rate (bpm), 
respiratory rate (pmi)] 
• 
Evaluation of the use of concomitant medications 
• 
Global Assessment of the Research Physician (graded scale of 10 points) 
• 
Efficacy and general tolerability assessed by the Medical Investigator 
• 
Routine laboratory tests 
• 
Imaging tests (MRI, CT, EEG) at medical discretion. 
 
 
 
 
  

 
 
 
 
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Risks 
The risks to research participants are the 
adverse effects associated with the study 
drug, according to the product package 
leaflet: mild gastrointestinal disorders 
(bloating, 
stomach 
pressure), 
and 
headache. Occasionally  heartburn, contact 
dermatitis, hypotension and, at very high 
dosages, dyspeptic symptoms. 
 
 
Benefits 
Immediate benefit is symptomatic chronic 
kinetosis improvement. Secondary benefit 
is knowledge increase on the use of the 
combination gamma-aminobutyric acid 
tartrate 100mg, glutamic acid 100mg, 
dibasic calcium phosphate 50mg, thiamine 
nitrate 25mg, pyridoxine hydrochloride 
10mg and cyanocobalamin 5mcg as well as 
Zingiber officinale dry extract 160mg  (8mg  
gingerols)  in the management of vertigo, 
nausea, and anxiety associated with 
kinetosis. 
 
 
5. OUTCOMES 
5.1 Primary outcome 
The primary outcome will  be the percentage of participants showing improvement >2 points in 
the MSAQ of Travel  2, Travel 3 and Travel 4 in relation to the pre-treatment score  (Travel 1). 
5.2 Secondary outcomes 
The secondary  outcomes  include: 
– 
The percentage of participants  showing  improvement in the subscores of the MSAQ 
of Travel 2, Travel 3 and Travel 4 in relation to the pre-treatment score (Travel 1). 
– 
The percentage of participants who presented adverse events related to the study 
medication. 
– 
Average values of pre- and post-treatment according to Physician Evaluation scores. 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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6. Schedule 
 
 
Activity 
Date 
Literature review 
May -July 2021 
Design of the project 
July 2021 
Research Ethics Committee  
August 2021 
Data collection 
October 2021  -  October  2022 
Data analysis 
November 2022 
Final report 
December 2022 
Submission for publication in a journal 
January 2023  -  February  2023 
 
7. Ethical Issues 
Participants who agree to participate in the study will undersign the Free and Informed Consent 
Form (Annex) in accordance with resolution 466/12 of National Health Council. Main 
investigator and his/her associates are aware of and will comply with the requirements of 
Resolution 466/12 of the National Health Council and its supplements and the Code of Medical 
Ethics of 1988 (Article 130). The former ones as well as the rest of the health team are commited 
in maintaining the privacy and confidentiality of the data from the participants'medical records, 
fully preserving the their anonimity. The data collected in the medical records will be used solely 
for the purpose informed in this protocol. Similarly, the variables generated by the study can 
only be used for the project purposes . 
8. Budget 
The study will be sponsored by the Gross Pharmaceuticals under the form of medicines supply, 
administrative support material, copying, printing, laboratory and imaging tests, transportation,  
published articles and books as well as statistical support.  
9. Researchers  
Main Investigator:  Prof. Carlos Pereira Nunes 
Associate Investigator: Prof.  Claudio Rodrigues 
 
 
 
 
 

 
 
 
 
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Annex. Free and Informed Consent Term 
FREE AND INFORMED CONSENT TERM FOR PATIENTS  DIAGNOSED WITH KINETOSIS   
Research Project "Double Blind Clinical Evaluation on the combination of Gamma-Aminobutyric 
Acid Tartrate 100mg, Glutamic Acid 100mg, Dibasic Calcium Phosphate 50mg, Thiamine Nitrate 
25mg, Pyridoxine Hydrochloride 10mg and Cyanocobalamin 5mcg compared to Ginger Extract 
as adjuvant therapy in symptomatic control of chronic vertigo motion sickness ". 
Study Site:  
Main Investigator:  
Patient Data: 
• 
Full Name: ______ 
• 
Date of Birth: (day/month/year) ____/____/__________ 
• 
Phone: ________ 
Attending Physician: _____ 
 
AUTHORIZATION 
You are being invited to participate in a research project on kinetosis (motion sickness). This 
disease correspond to a set of symptoms of malaise associated with movement, especially during 
travel in cars, trains, buses and ferries. During this research,  you will be asked to answer a 
questionnaire evaluating the presence and severity of kinetosis symptoms before and after 
treatment with ginger extract or a combination of gamma-aminobutyric acid, glutamic acid 
calcium, thiamine, pyridoxine and cyanocobalamin. First, you will take a journey of at least 15 
minutes without the treatment and answer the questionnaire afterwards. Then, you  will start 
taking the study tablet  every  8  hours  (3 times  a  day) for 7 days making your routine trips of 15 
minutes duration minimun and after each travel you will answer the questionnaire again. This  
questionnaire  should be  completed on three different occasions, that means, after three trips. 
You will also be asked to write down the date of each trip and the time of travel.   
 I understand that I will have no compensations in exchange of my participation, as well as any 
family member,son, daughter, or anyone else. 
   I had the opportunity to ask questions about the procedures of this clinical investigation and to 
reflect on the answers I have been given.  
 I understood that participation in this clinical investigation is voluntary, that I can quit anytime, 
and that leaving this investigation would not compromise my clinical follow-up. I know that the 
doctor responsible for the study is Prof. Carlos Nunes and that I can ask him questions in the clinic 
or by phone. 
 I authorize the use of the information on me contained in my medical chart, which will be used 
only for the purposes of this clinical research, will not be used in other studies without a new 
authorization, and which will be kept confidential (secret) regarding my identification.  
 

 
 
 
 
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I, _________  agree to participate in this clinical investigation.  
 
I confirm that I have explained the nature of this investigation to the patient. 
 
Physician Signature: _____ 
 
Witness Signature: _______ 
 
Signature Date: ____/____ 
 
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