Clinical trial NCT03811366
Conditions: Uveomeningoencephalitic Syndrome Inflammation Choroid Disease Visual Impairment
Sponsor: University of Sao Paulo
Start date: 2011-06-01; Completion date: 2017-01-31
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Patients with acute onset Vogt-Koyanagi-Harada disease (VKHD) were prospectively included in this study. They were systematically followed with clinical, posterior segment imaging exams and full-field electroretinogram during a minimum 24-month of follow-up. All patients were treated with 3-day methylprednisolone pulse therapy followed by 1mg/day oral prednisone with a slow tapper during a median of 13 months. Non-steroidal immunosuppressive therapy (IMT) was introduced in cases of refractory disease or in cases of prednisone intolerance. Outcome measured by full-field electroretinogram was analyzed and patient was grouped as electroretinogram stable or electroretinogram worsening. Clinical data was analyzed in these two electroretinogram-based groups.

Detailed description:
Consecutive patients with acute onset VKHD were included and followed for a minimum 24-month as Part I of an ongoing prospective long-term study on VKHD. The main purpose was to understand the course of clinical and subclinical choroidal inflammation in patients receiving early and high-dose corticosteroid followed by high-dose oral prednisone and a very slow tapper. All patients were followed with clinical and posterior segment imaging (PSI) exams, i.e. fundus picture, fluorescein angiography, indocyanine green angiography and enhanced depth imaging optical coherence tomography, at inclusion, 1st month, and thereof every three months. Full-field electroretinogram was performed at inclusion, 1st month, and thereof every six months. Flare was defined as appearance or increase/worsening of inflammatory signs after the initial six-month from disease onset during the predefined treatment protocol. Inflammatory signs were cells in anterior chamber, macular edema; subclinical inflammatory signs were mainly those observed by PSI exams. Scotopic full-field electroretinogram results between 12 and 24 month were the main outcome. Clinical data was analyzed in the full-field electroretinogram-based groups.

Arms: arm 1: All patients in the acute phase will be treated with corticosteroid monotherapy, unless presents a contraindication or persistence/ recurrence of inflammation with regressive corticosteroid monotherapy.This is the unique arm of the present study.

Treatment protocol includes a three-day course of intravenous methylprednisolone (1000 mg per day) followed by a high dose of oral prednisone (1.0 mg/kg/day) with a slow tapering with dose equal or less than 0.1mg/kg/day after 10 months. The prednisone dose is scheduled to be reduced in a 0.1 mg/kg-step ladder until it reaches 0.3 mg/kg (i.e. for an individual with 60 kg, dose would be 20 mg): from 1 to 0.8 mg/kg every two to three weeks; at 0.7 mg/kg for 4 weeks; at 0.6 mg/kg for two to three weeks; from 0.5 mg/kg every 4 weeks; from 0.3 to 0.15 mg/kg every 6 weeks; and 0.1 mg/kg, 0.075 mg/kg and 0.05 mg/kg for 8 weeks each.
Interventions: intervention 1: Corticosteroid monotherapy
Intervention descriptions: intervention 1: Patients will receive corticosteroid monotherapy as a pulsetherapy (1000mg/ day for 3 days) followed by oral corticosteroid.

Protocol documents:
Prot_SAP_002.pdf: 
 
 
 
Multimodal Analysis and 
Electroretinogram in VKH 
From Acute Onset - Part I 
 
NCT03811366 
 
03/26/2025 
 
 
 
 


STUDY PROTOCOL  
Prospective cohort study on VKH disease conducted from June 2011 through 
January 2017 at Uveitis Service, Hospital das Clinicas HCFMUSP, Faculdade de 
Medicina, Universidade de Sao Paulo, SP, BR. The local institutional review board 
approved the full protocol, which follows the tenets of the declaration of Helsinki 
(clinicaltrials NCT03811366).  
The inclusion criteria consisted of: diagnosis of VKH disease in the acute phase 
according to the International Committee in 2001 [1]. The exclusion criteria were: less 
than a 24-month follow-up period and contraindication to corticosteroid therapy. 
Treatment protocol included a three-day course of intravenous methylprednisolone 
(1000 mg per day) followed by a high dose of oral prednisone (1.0 mg/kg/day) with a 
slow tapering with dose equal or less than 0.1mg/kg/day after 10 months. The 
prednisone dose was scheduled to be reduced in a 0.1 mg/kg-step ladder until it reaches 
0.3 mg/kg (i.e., for an individual with 60 kg, dose would be 20 mg): from 1 to 0.8 
mg/kg every two to three weeks; at 0.7 mg/kg for 4 weeks; at 0.6 mg/kg for two to three 
weeks; from 0.5 mg/kg every 4 weeks; from 0.3 to 0.15 mg/kg every 6 weeks; and 0.1 
mg/kg, 0.075 mg/kg and 0.05 mg/kg for 8 weeks each. Oral corticosteroid dose increase 
was prescribed in case of persistent clinical inflammation signs in two steps and at least 
0.5 mg/kg/d. For example, if a patient with 60 kg presents worsening of inflammatory 
signs while in use of 0.4 mg/kg/d, oral corticosteroid should be increased to 0.6 
mg/kg/d. On the other hand, if a patient with 60 kg presented a clinical flare while using 
0.2 mg/kg/d, the oral corticosteroid should be increased to at least 0.5 mg/kg/d. 
Subsequent tapering would be performed as previously scheduled. Additional non-
steroidal immunosuppressive therapy (IMT) would be prescribed if the patient 
presented intolerance due to side effects (e.g., psychosis) or prednisone monotherapy-
refractory inflammation. IMT use would be considered as an additional therapy if 
implemented for at least six months and if includes cyclosporine A, azathioprine, or 
mycophenolate mofetil. 
Examinations were performed at inclusion, 1, 2, 4, 6 months (M), and, thereafter, 
every 3 months. Each visit included complete clinical and imaging examinations (e.g., 
fundus color photography, ICGA, fluorescein angiography – FA and EDI-OCT). ff-
ERG was performed at inclusion; at 30 days and at 6 months intervals thereafter, using 
RETI-port system (Roland Consult; Electrophysiological Diagnostic Systems, 
Brandenburg, Germany). Fundus color photography was performed using the Topcon 


TRC-50DX (Tokyo, Japan); FA, ICGA and EDI-OCT were performed using 
Spectralis® HRA+OCT (Heidelberg Engineering, Germany). Fundus findings were 
graded according to a previously described analytical framework [2]. The development 
of sunset glow fundus was classified as either present or absent based on the fundus 
color photography. Imaging examinations were read by two well-trained examiners. In 
case of instances of disagreement, the senior reader would classify the images and 
would be responsible for the final decision. The FA and ICGA reading charts were 
adapted from Tugal-Tutkun et al [3]. Dark dots (DD) were evaluated based on a semi-
quantitative score for the posterior pole and each quadrant: sparse and/or faint and 
numerous and/or pronounced. The total score varies from 0 to 8. Fluctuation was 
defined as a change in DD quantity (e.g., sparse to numerous or vice versa) according to 
the Tugal-Tutkun et al score and whether the DD in the posterior pole or in each 
quadrant [3]. Objectively, DD fluctuation was defined as a final score variation ≥ 0.5 
between two different points in time. ff-ERG recordings were performed in accordance 
with the International Society for Clinical Electrophysiology of Vision guidelines with 
the RETI-port system (Roland Consult) using ERG-jet electrodes (Universe SA, La 
Chaux-deFons, Switzerland) [4]. Scotopic ERG responses were recorded after a period 
of 20 minutes of dark adaptation, and photopic ERG responses were recorded after 10 
minutes of light adaptation. The recording sequence was scotopic rod response, scotopic 
cone–rod combined response, scotopic oscillatory potentials, photopic cone response, 
and 30-Hz flicker cone response. The normal value limits for each specific ERG 
response were established at 95% confidence intervals. Amplitude and implicit time of a 
and b wave of eight averaged stimulus response for each phase were analyzed, and the 
results were compared with a normative database. The worsening of the ERG 
parameters was defined as value reduction  30% in any scotopic ERG parameter, 
which needed to be confirmed in two consecutive examinations [5]. ff-ERG scotopic 
parameters obtained at 12 and 24 months were compared; all included eyes were 
grouped based on the worsening or stabilization of the scotopic parameters from 12th to 
24th month.  
After the acute inflammatory phase (six months following disease onset), disease 
activity was systematically evaluated based on both clinical and subclinical signs. 
Specifically, clinical signs included anterior chamber cells (ACC) of at least 1+ cells, 
exudative retinal detachment, and macular edema confirmed on FA and/or OCT. Visual 
acuity measurement with a Snellen chart was converted to LogMAR values. Subclinical 


signs are those detected exclusively in posterior segment imaging (PSI) and included 
optic disc leakage/hyperfluorescence (ODH) and/or perivascular leakage on FA; 
hypofluorescent DD on ICGA; and, increase of at least 30% in subfoveal choroidal 
thickness (CT) in two consecutive EDI-OCT examinations. Perivascular leakage was 
observed as an increase in hyperfluorescence around retinal vasculature over time on 
FA exam at midperiphery. Isolated subclinical signs of activity did not infer change in 
treatment schedule, whereas clinical signs led to either an increase in a daily oral 
prednisone dosage of 0.2 mg/kg (up to at least 0.5 mg/kg/day) or the introduction of 
non-steroidal IMT (i.e., azathioprine, cyclosporine, or mycophenolate mofetil). Any 
intolerance to corticosteroid also determined a switch in treatment to non-steroidal IMT. 
Based on the predefined protocol, the term “flare” was used to describe the appearance 
or worsening of inflammatory signs observed at least sixth months after disease onset. 
During the 24-month follow-up period, the presence of ocular complications (i.e., 
cataract [6], ocular hypertension/glaucoma [7,8], choroidal neovascularization (CNV) 
[9], or SGF) was recorded. Cataract was defined as any lens opacification greater than 
nuclear or cortical 2+/4 or subcapsular 1+/4 [6]. Ocular hypertension was defined as an 
intraocular pressure (IOP) above 21mmHg [7,8]. The CNV membrane was diagnosed 
when increasingly localized hyperfluorescence at the posterior pole is detected on FA or 
a hyperreflective subretinal lesion associated with sub or intraretinal fluid on OCT. 
The main outcomes measures included clinical and subclinical flares, presence of 
sunset glow fundus, and ff-ERG results from 12 to 24 months of follow-up. 
 
STATISTICAL ANALYSIS PLAN WITH RESULTS INFORMATION 
Twelve patients (24 eyes, 10 female) with acute VKH disease were included in the 
study. For descriptive data analysis, medians and ranges were calculated. Table 1 
summarizes the data regarding clinical and subclinical signs of inflammation, 
complications and ff-ERG results during the 24-month follow-up.


 
 
 
 
 
 
 
 
 
 
 
 
 


For the comparison of qualitative and quantitative data between the stable ERG and 
worsening ERG groups, the Fisher exact test and Mann Whitney test, respectively, was 
used (Tables 2 and 3). Furthermore, Kappa statistics was used to test interrater 
reliability between subnormal ERG and SGF. P values ≤ 0.05 were considered 
statistically significant. Generalized estimated equations (GEE) were used for analyzing 
binary ocular data. (Tables 2 and 3) Data analysis and statistical tests were conducted 
using SPSS 20.0 (SPSS Science, Chicago, IL, USA).  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 


 


REFERENCES  
[1] R. W. Read et al., “Revised Diagnostic Criteria for Vogt-Koyanagi-Harada Disease: Report 
of an International Committee on Nomenclature,” Am. J. Ophthalmol., vol. 131, pp. 647–652, 
2001.  
[2] F. T. da Silva, C. E. Hirata, E. Olivalves, M. K. Oyamada, and J. H. Yamamoto, “Fundus-
based and electroretinographic strategies for stratification of late-stage Vogt-Koyanagi-Harada 
disease patients. Am J Ophthalmol 148(6):939–945  
[3] I. Tugal-Tutkun, C. P. Herbort, and M. Khairallah, “Scoring of dual fluorescein and ICG 
inflammatory angiographic signs for the grading of posterior segment inflammation (dual 
fluorescein and ICG angiographic scoring system for uveitis).,” Int. Ophthalmol., vol. 30, no. 5, 
pp. 539–52, Oct. 2010.  
[4] D. L. McCulloch et al., “ISCEV Standard for full-field clinical electroretinography (2015 
update),” Doc. Ophthalmol., vol. 130, pp. 1–12, 2015.  
[5] E. L. Berson et al., “Natural Course of Retinitis Pigmentosa Over a Three Year Interval,” 
Am. J. Ophthalmol., vol. 99, no. 3, pp. 240–251, 1985.  
[6] L. T. Chylack, J. K. Wolfe, D. M. Singer, M. C. Leske, M. a Bullimore, and L. Ian, 
“Opacities Classification,” Arch. Ophthalmol., vol. 111, pp. 831– 836, 1993.  
[7] D. A. Jabs, R. B. Nussenblatt, J. T. Rosenbaum, and Standardization of Uveitis 
Nomenclature (SUN) Working Group, “Standardization of Uveitis Nomenclature for Reporting 
Clinical Data. Results of the First International Workshop,” Am. J. Ophthalmol., vol. 140, no. 3, 
pp. 509– 516, Sep. 2005.  
[8] P. J. Foster, R. Buhrmann, H. a Quigley, and G. J. Johnson, “Prevalence Surveys,” Br J 
Ophthalmol., pp. 238–243, 2002.  
[9] C. M. R. Adán A, Mateo C, Navarro R, Bitrian E, “Intravitreal bevacizumab (avastin) 
injection as primary treatment of inflammatory choroidal neovascularization.,” Retina, no. 9, pp. 
1180–1186, 2007. 
 

ICF_003.pdf: 
Multimodal Analysis and 
Electroretinogram in VKH From 
Acute Onset – Part I  
 
 
NCT03811366  
 
 
 
 
19/04/2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
03/26/2025


 
 
2 
2 
 
HOSPITAL DAS CLÍNICAS DA 
 FACULDADE DE MEDICINA DA UNIVERSIDADE DE SÃO PAULO 
INFORMED CONSENT FORM 
I - IDENTIFICATION DATA OF THE RESEARCH SUBJECT OR LEGAL RESPONSIBLE 
1. NAME .:.......................................................................................................................... 
IDENTITY Nº : ........................................ SEX :    M Ž    F Ž   
DATE OF BIRTH: ......../......../......  
ADDRESS ................................................................................. Nº ...........................  
CITY  ............................................................. 
POSTAL CODE:...............................TELEPHONE (............) ...................................................................... 
2.LEGAL RESPONSIBLE .............................................................................................................................. 
IDENTITY :....................................SEXO:  M Ž    F Ž    
DATE OF BIRTH: ......../......../......  
ADDRESS ................................................................................. Nº ...........................  
CITY  ............................................................. 
POSTAL CODE:...............................TELEPHONE (............) ...................................................................... 
II – DATA ABOUT THE RESEARCH 
1. MULTIMODAL ANALYSIS AND ELECTRORETINOGRAM IN VKH FROM ACUTE ONSET 
2. RESEARCHER: Dra. Joyce Hisae Yamamoto Takiuti 
FUNCTION: Assistant Physician/Researcher 
REGIONAL COUNCIL REGISTRATION Nº: 51804   
HCFMUSP UNIT: OPHTALMOLOGY CLINIC 
3. RESEARCH RISK ASSESSMENT: 
 
NO RISK 
Ž  
 
MINIMUM RISK 
X 
 
MEDIUM RISK Ž  
 
LOW RISK 
Ž  
 
GREAT RISK 
Ž  
(Probability that the individual will suffer some harm as an immediate or delayed consequence of the study) 
4. RESEARCH DURATION: 2 years 
 
III - REGISTRATION OF EXPLANATIONS BY THE RESEARCHER TO THE PATIENT OR THEIR 
LEGAL REPRESENTATIVE ABOUT THE RESEARCH CONSIGNING: 
1. Rationale and research objectives 
You are being invited to participate in a clinical trial involving people with Vogt-Koyanagi-Harada disease. Please 
read this informed consent form carefully and ask any questions you may have before deciding whether to participate in 
the study. Your decision to consent to participate in this study is voluntary and you may withdraw from the study at any 
time. If you decide not to participate or to withdraw from the study, you will not lose benefits to which you would otherwise 
be entitled. You will be informed about any new information that may arise during the research that may change your 
willingness to participate in this study. Your doctor may discontinue your participation in this study, regardless of your 
consent, if he/she considers this to be the best course of action in your particular case. 
2. Information about your disease and research objectives 
Vogt-Koyanagi-Harada disease is a disease that affects structures that have melanin pigment in common. Thus, the 
disease affects the skin, ears, meninges and, mainly, the eye. This disease, if diagnosed early and treated properly, results 


 
 
3 
3 
in good vision recovery. However, in some patients the inflammation does not go away easily and it remains for long 
periods (months) and in others the inflammation disappears completely but recurs after some time (months to years).  
The cause of Vogt-Koyanagi-Harada still does not have a defined cause, but it is known that it is the result of “self-
harm”. In other words, the patient's immune system, which has a primary function of defense against foreign and external 
organisms, attacks proteins present in the organism itself, causing the disease. In general, it occurs in people who have a 
genetic tendency to this "self-injury". 
In this study we will perform several tests routinely used to assess the extent and activity of this disease. We will also 
do some laboratory tests with the material obtained from your blood sample to analyze the possible causes of this disease 
and why some patients have the disease in a more severe form. 
If necessary, treatment to control the disease will be used and the effects on the eye and body will be monitored. 
Laboratory tests will be carried out with material obtained from your blood sample to control the effects of systemic 
medication on the body, if used. 
3. Procedures that will be used and purposes, including identification of procedures that are experimental 
The tests to be carried out will tell us how your visual function is. So, we will first document the changes found in 
your eye by taking pictures of your fundus (retinography). Autofluorescence is another type of photography using different 
types of light (infrared light and blue light). Changes in the vessels of the various layers of the eye will be studied using 
two types of dyes that will be injected into your vein. These dyes circulate through the body and the eye, and facilitate the 
observation of changes caused by the disease in the back of the eye (angiography with fluorescein and indocyanine). 
Photos will be taken for documentation and better evaluation of the fundus with contrast. 
Furthermore, to document the changes in your eye fundus, we will perform a retinal tomography (optical coherence 
tomography). Optical coherence tomography uses invisible light to produce very detailed images of the fundus. No dye is 
injected and there is no contact with your eye by the device. 
To assess how much these changes are harming your vision, an electrophysiological examination of the retina will 
also be performed (similar to the electroencephalogram examination of the “head”). These exams require a lot of your 
attention and last around thirty minutes each. 
None of these tests are experimental and are routinely used in the evaluation of patients with “back of the eye” 
problems. 
Blood samples will be collected with a volume of 10ml with two objectives: 1. determination of the “blood type”, if 
you are predisposed to this disease or not, 2. identify possible changes that medications in use may cause in your body. 
4. Expected discomforts and risks 
The expected risks in this study are minimal. All exams to be performed are already part of the international 
ophthalmological practice. 
Some tests involve touching the eye with devices (ultrasound and electroretinogram) and, despite the eye being 
previously anesthetized, slight discomfort can be expected.  
Tests using contrast (fluorescein and indocyanine angiography) can trigger mild, moderate, or, less commonly, severe 
side effects. The most common reaction is nausea (1-15% of cases) and eventually vomiting immediately after contrast 
injection. They are, in general, of short duration and the relief happens naturally or with the use of medication normally 
used for nausea. The most common moderate reactions are hives (allergic skin reaction with itching and redness) and 
fainting. There is also the remote possibility of generalized contrast allergy – about 1 in every 10,000 exams. It is important 
to report any allergies to medications, iodine and especially to the ingestion of seafood to the doctor responsible for your 
examination. These previous allergies can help predict whether you are more likely to develop this type of reaction. Severe 
allergies can be managed with medication. Life-threatening, however, can happen in rare cases. In case of suspected 
pregnancy, it is important to inform the doctor before the procedure is carried out. There may be dark pigmentation of 
urine and sweat in the days following the examination, without remaining this way for more than 2 or 3 days. 
As for the punctures to collect your blood, there may be a slight discomfort from the puncture for peripheral venous 
access and removal of a small amount of peripheral blood. There may be a slight local hematoma. 
In order to carry out these exams, you will need to attend on pre-scheduled dates. You must be accompanied to take 
photographs of the fundus of the eye due to the need for eye dilation. This dilation of the pupil leads to momentary visual 
difficulty, which is why we recommend that you are accompanied when you return home. In addition, we will have 
consultations for clinical evaluation that will be scheduled on dates that are suitable for you and the medical team. Your 
attendance to perform all procedures is essential for the best monitoring of your disease and the good progress of the study. 
Therefore, it is important that you agree and commit to attend, unless you have justifiable reasons for not attending. 
The use of medications to control the disease carries a minimal risk of side effects. The prescription of these drugs 
will only be carried out when it is really necessary to control the eye disease. Both intravenous corticosteroid therapy to 
be used in the acute phase, and immunosuppressants, such as cyclosporine and azathioprine, to be used in the chronic 
phase, are widely accepted and used in the international medical community. None of these medications are experimental. 


 
 
4 
4 
The main side effect described for cyclosporine is kidney toxicity, which especially affects patients over 55 years of 
age. Azathioprine can cause toxic effects on the liver and decrease in blood cells. The most common short-term side effects 
of intravenous corticosteroid therapy are potassium loss, bloating, weight gain, transient increase in blood glucose, nausea, 
stomach pain, acne, mood swings, insomnia, and metallic taste in the mouth. Some other side effects of corticosteroids: 
high blood pressure, increased lipids (fats) in the blood, osteoporosis, muscle injuries, cataracts, glaucoma, cardiac 
arrhythmias, thrombus formation (which can “clog” blood vessels), psychiatric symptoms (depression, insomnia and 
psychosis) and infections. 
All these side effects will be carefully controlled by the responsible medical team through clinical and blood tests. 
Any eventual complications will be treated. It is important to remember that the benefit you will have with the use of a 
certain medication will always be considered greater than the risk of you presenting any of the side effects described, since 
no medication is being tested and the objective is your improvement. 
5. Benefits that can be obtained 
Vogt Koyanagi Harada disease is a chronic disease that can evolve slowly, in outbreaks, leading to worsening vision. 
The tests to be performed allow for a more accurate assessment of patients and their illness and will be performed in a 
standardized manner (at regular intervals). With this we want to provide you with an ideal follow-up and better treatment 
in order to prevent the evolution of your disease. 
There is no financial compensation to study participants. 
6. Alternative procedures that may be advantageous to the individual 
There are several forms of treatment for Vogt Koyanagi Harada disease. However, there is no absolute standard or 
considered “the best”. The treatment of the acute phase of the disease always uses corticosteroids, which can be 
administered orally (through the mouth) or intravenously (through a vein). Both present the risk of developing major or 
minor side effects according to the characteristics of each patient. As previously explained, the researchers believe that 
vein therapy can bring greater benefits to the patient and this is the form of treatment of choice for acute cases. 
 
IV. CLARIFICATIONS GIVEN BY THE RESEARCHER ABOUT RESEARCH SUBJECT 
GUARANTEES CONSIGNING 
1. 
Access, at any time, to information on procedures, risks and benefits related to the research, including to resolve 
any doubts. 
You will be able to have access to any information and any doubts about your case and all the exams that are being 
carried out, through your doctor. 
 
2. 
Freedom to withdraw your consent at any time and to stop participating in the study, without prejudice to the 
continuity of care. 
Your participation in this study is completely voluntary. You will not lose health care benefits that you would 
otherwise have if you decide not to participate or if you withdraw from participating in the study at any time. 
 
3. 
Safeguarding Confidentiality, Secrecy and Privacy. 
Any information collected is strictly confidential. Your name will never be revealed in the study reports and your 
identity will not be communicated to third parties, and can only be provided to physicians involved in this research. 
The data obtained in the research may be used for future publications, respecting their confidentiality. 
 
4. 
Availability of assistance at HCFMUSP, for any damage to health resulting from the research. 
Any damage to your health resulting from the research will be assisted in this Hospital at no cost. A research-related 
health problem is considered when it has been caused by the procedures required by the research. 
 
V. INFORMATION ON NAMES, ADDRESSES AND TELEPHONE NUMBERS OF RESPONSIBLE 
PERSONS RESPONSIBLE FOR FOLLOWING THE RESEARCH, FOR CONTACT IN CASE OF CLINICAL 
INTERCURRENCES AND ADVERSE REACTIONS. 
 
Dra Viviane Mayumi Sakata– Telephone: (41) 8826-3757  
 
 
 
 


 
 
5 
5 
VI - POST-CLARIFIED CONSENT 
I declare that, after being conveniently clarified by the researcher and having understood what was explained to me, I 
consent to participate in this Research Protocol. I also authorize the storage of samples from the collection approved by 
this consent form for use in future research, according to Resolution No. 347, of January 13, 2005, of the National Health 
Council 
. 
  
São Paulo,                    de                            de 200        . 
__________________________________________            Signature of the research subject or legal guardian 
 
__________________________________________            Researcher signature