This form is designed for the NIMAD-INSF Call for Proposal (1 Mordad- 20 Shahrivar 1400) ONLY.

For other calls, please check out NIMAD and INSF’s websites

Pre-Proposal Application Form

‫ خواهشمند است جهت کسب اطالع از ضوابط فراخوان به لینک‌های زیر مراجعه‬،‫عضو محترم هیأت علمی‬
:‫نمایید‬
:)NIMAD(‫ ضوابط فراخوان در مؤسسه ملی توسعه تحقیقات علوم پزشکی ایران‬-
‫برای اعضای هیأت علمی‬http://nimad.ac.ir/content/224/NIMAD-INSF-140005 ‫به نشانی‬
‫دانشگاه‌های علوم پزشکی‬
:)INSF(‫ ضوابط فراخوان در صندوق حمایت از پژوهشگران و فناوران کشور‬-
‫ برای اعضای هیأت علمی سایر دانشگاه‌ها‬http://insf.org/fa/news/203 ‫به نشانی‬
‫در نظر داشته باشید تکمیل و ارسال این فرم به منزله مطالعه دقیق راهنمای متقاضیان این فراخوان در هر‬
.‫دو وب‌‌سایت‌ فوق و پذیرش اقدام در موارد مندرج در راهنما است‬
‫ است و‬۱۴۰۰ ‫ شهریورماه‬۲۰ ‫الزم به ذکر است مهلت ارسال پروپوزال اولیه در این فراخوان اول مردادماه لغایت‬
.‫تمدید نخواهد شد‬

General Information

NIMAD’s Electronic Application No. *

INSF’s Electronic Application No. *

Effect of combined KCa channel blocker -

Senicapoc- and Kv1.3 channel blocker
Research Project Title
telmisartan-on neurological and inflammatory
status of COVID-19 patients
NIMAD Applicant’s Full Name (Principle
Fardin Faraji
Investigator, PI)

INSF Applicant’s Full Name (Principle

Saeed Tahmasebi
Investigator, PI)
Health Technology (Medicine, Implants, Medical Equipment,
Diagnostic Tools & Biosensors, Micro-robots, Bionics &
Wearables)
Artificial Intelligence, Machine Learning & Big Data in Disease
Diagnosis, Prevention & Treatment
Theme (Please choose the best match) Environmental Pollutants (Identification, Impact Assessment &
Control)
Biomaterial in Medicine, Tissue Engineering, Printers, Bio-inks &
3D Products
Food Safety & Hygiene, & Probiotics

* Please write down the proposal number provided by NIMAD and INSF electronic submission system, based on the
system that you have to use.
 Justification of the Project

Approach (500-800 words):

Describe your methods further than what you have provided in the online abstract (the abstract completed on NIMAD
and INSF’s electronic submission system), ideally for each aim separately.
If applicable, explain the nature of your variables, research design, your measurement tools, sample size calculation,
subject recruitment strategies, data collection and analysis methods.
This is also known as “Material and Methods
In this randomized controlled clinical trial, defined cases of COVID-19 with mild and moderate
pneumonia (according to the NIH guideline) will be treated with conventional treatment regimens
(controls) as well as in combination with oral administration of Telmisartan plus Senicapoc
(intervention arm). After randomization, each group will be received the mentioned treatments
and were evaluated for different variables including mortality, hospitalization duration, intensive
care unit (ICU) administration ratios as well as laboratory variables such as leukocytes and
lymphocytes count. The follow-up period considered as 2 weeks after discharge. The mentioned
variables were assessed as before and after receiving the treatment in each group as well as
intergroup analysis for comparing both baseline and final values.
Inclusion Criteria:
Defined cases of COVID-19 based on laboratory and/or radiological and clinical manifestation
Exclusion Criteria:
Age <10, Pregnancy, Severe kidney dysfunction, Previous history of allergy to Colchicine, not
willing to sign informed consent form
The dose levels are 30 mg of the investigational drug, Senicapoc (single dose) and Telmisartan
(80 mg twice daily, oral administration) for 7 days.
For this study one week treatment is suitable for COVID-19 induced cytokine storm inhibition.
Circulating cytokine levels (IL-2, IL-4, IL-10, IFN-γ, IL-6, TNFα) and biomarkers of
inflammation (C-reactive protein, CRP and procalcitonin, PCT) will be examined over the
disease course.

Neurological outcomes: Myalgia, taste impairment, smell impairment, headache, dizziness, and
encephalopathy. anosmia, ageusia, periorbital pain, dizziness, fatigue, even moderate headache,
moderate memory and/or behavioral disorders.

Other symptoms will be monitored in this study: blood glucose, insulin tolerance test, olfactory
disorders, Locomotor activity, Sickness behavior, Depression and Anxiety.
Outcome Measures :
Mortality Rate [ Time Frame: From admission to 14 days after being discharge. ]
All cause of death in duration hospitalization
Secondary Outcome Measures:
SpO2 [ Time Frame: Admission to discharge dates (approximately 4-14 days after admission).
Discharge variables considered as the last available data before their death for the expired
patients. ]Change in patients' oxygen saturation levels assessed by non-invasive method (pulse
oximetry)
Length of Hospitalization [ Time Frame: The duration of hospitalization for the patients
(admission to discharge dates, approximately 4-14 days after admission). The patients who died
were excluded.]
Day(s) each patient has spent in the hospital as an inpatient.
Lymphocyte Count [ Time Frame: Admission to discharge dates (approximately 4-14 days after
admission). Discharge variables considered as the last available data before their death for the
expired patients. ]
Lymphocyte count*1000/ mm^3
Decrease of inflammatory cytokines level.

2
Significance and Expected Outcomes (200-300 words):
Provide an overview of existing knowledge and gaps in knowledge directly related to your aims, ideally indicate for
each aim separately.
Justify why it is critical to fund your research project and explain how it will expand the body of science, and how its
findings can be used to inform health policy and practices.
Indicate if outcome of your research can lead to a development of a product or service!
Check out NIMAD’s video on Aparat

The excessive inflammatory response during COVID-19 is the major cause of death in these
patients, leading to the use of a series of immunomodulatory agents into clinical trials but also in
an off-label manner. However, from a therapeutic point of view, we must choose drugs that not
only blunts the NF-κB/NLRP3 inflammasome connection during infection, but also that combat
the oxidative stress response causing pulmonary and systemic damage.
These twodrugs, are likely to be effective against the consequences of the elevated levels of
cytokines (including interferon-γ) typically observed in people with COVID-19
(2). Ca2+-activated potassium channels (KCa channels) constitute a heterogeneous family of ion
channels with variable biophysical and pharmacological properties. These channels share a
common functional role by coupling the increase in intracellular Ca2+ concentration to
hyperpolarization of the membrane potential. This intrinsic feature allows KCa channels to play
key roles in controlling cellular excitability and maintaining K+ homeostasis and cell volume in
non-excitable cells.
The FDA has granted a rare pediatric disease (RPD) designation to the novel p-STAT3 inhibitor
WP1066 for the treatment of patients with the rare brain and spinal cord malignancy,
ependymoma, according to a press release from the developer.
Senicapoc is more potent on KCa3.1and more selective over other related KCa or more distantly
related KV, NaV and TRP channels.

Innovation (100-200 words):

Explain how your research project will challenge and seek to shift current research or clinical practice paradigms by
utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions.

3
Built from the chemical backbone of the active ingredient in propolis, a natural product of honey
bees, WP1066 is the first anticancer agent with drug-like properties that consistently inhibits the
activated form of STAT3 within cancer cells, a target that has been long-sought because of its
broad range of tumor promoting effects. Importantly, activated STAT3 supports the survival and
proliferation of tumor cells, evasion of the immune response and metastasis to distant organs, as
well as angiogenesis (growth of blood vessels) essential for tumor growth. Activated STAT3 is
not only connected with directly supporting tumor activity, but also suppressing the immune
system that is novel for COVID-19 treatment.

References (3-5):
1. Liu YS, Zhang D, Tang S, Chen H, Chen L, He X, Tong M, Liu M, Lin Y, Zhu B,
Su X The Epidemiological and Clinical Characteristics of 2019 Novel
Coronavirus Infection in Changsha, China. 2020.
2. Wang L, Gao YH, Lou LL, Zhang GJ. The clinical dynamics of 18 cases of COVID-19 outside
of Wuhan, China. Eur Respir J. 2020;55(4):2000398.
3. Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L. Selfreported olfactory and
taste disorders in SARS-CoV-2 patients: a crosssectional study. Clin Infect Dis. 020;71(15):889–
90
4. Xu X, Yu C, Qu J, Zhang L, Jiang S, Huang D, et al. Imaging and clinical features of patients
with 2019 novel coronavirus SARS-CoV-2. Eur J Nucl Med Mol Imaging.

4
 Budget Details*

Expenses and Costs NIMAD INSF

Please provide the numbers in million Rial. Year 1 Year 2 Year 3 Year 1 Year 2 Year 3 Total

Personnel ** 50
Equipment -
Consumables 350
Travel -
Publication -
Other -
Total (in million Rial) 400

Total Amount Requested from NIMAD (in million Rial) 200

Total Amount Requested from INSF (in million Rial) 200

Total Amount Requested/ Provided from other Resources (in million Rial) -

* The proposed budget should provide an accurate assessment of all costs; failure to do so
may result in fast rejection by NIMAD and/or INSF.
** NIMAD’s standard for personnel costs , INSF’s standard for personnel costs.

Details on Grants Relevant to this Proposal*

Mention all grants that either of the PIs has received during the past 5 years, on
research projects with relevant subjects to this proposal.
Funding
Organisation Total Budget
Project Title Name of PI
(university, research (million Rial)
institute, etc.)

-- - - -

* All recent projects relevant to this proposal must be declared; failure to do so may result
in fast rejection by NIMAD and/or INSF .

5
Statement on collaboration background and strength
Briefly describe the added value of the collaboration between the two principle investigators (PI)
(max. 500 words)
Added value may include but is not limited to: access to special expertise; research
facilities and/or equipment; data, techniques and/or skill sets; and Unique populations
and/or environments.

INSF investigator is expert in assay of paraclinical tests (immunological cytokines, olfactory

and behavioral disorders. NIMAD researcher will collaborate in patient selection and execution
of protocols.

Five Top publications over the last three years for NIMAD PI

Authors (in order). Title. Publication name. Year; volume: pages Journal’s
IF*

1- Faraji F, Mohaghegh P, Ravand HR, Javaheri J. Risk Factors Associated with Prognosis
in Patients with Acute Stroke: A Retrospective Observational Study. Iranian Red Crescent
0.427
Medical Journal. 2020 Dec 13;22(12).

2- Faraji F, Shojapour M, Farahani I, Ganji A, Mosayebi G. Reduced regulatory T

lymphocytes in migraine patients. Neurological Research. 2021 Apr 16:1-6. 2.401

3- Faraji F, Hashemi M, Ghiasabadi A, Davoudian S, Talaie A, Ganji A, Mosayebi G.

Combination therapy with interferon beta-1a and sesame oil in multiple sclerosis.
2.063
Complementary therapies in medicine. 2019 Aug 1;45:275-9.

4- Faraji F, Bayani M, Jafarpour M, Abdolalian F. Maxillary sinus floor augmentation and

simultaneous dental implant placement in a patient with Guillain‐Barre syndrome: A case
0.53
report. Clinical case reports. 2019 Dec;7(12):2331-5.

5-Dehghan L, Faraji F, Dalvand H, Shamsoddini A, Hadian-Rasanani MR. Occupational

performance of individuals with Multiple Sclerosis based on disability level in Iran. Iranian .40
journal of neurology. 2019 Jan 5;18(1):1.
Five Top publications over the last three years for INSF PI

Authors (in order). Title. Publication name. Year; volume: pages Journal’s
IF*

Tahmasebi S, Oryan S, Mohajerani HR, Akbari N, Palizvan MR. Probiotics and Nigella
sativa extract supplementation improved behavioral and electrophysiological effects of PTZ- 2.061
induced chemical kindling in rats. Epilepsy & Behavior. 2020 Mar 1;104:106897.
Goudarzvand M, Panahi Y, Yazdani R, Miladi H, Tahmasebi S, Sherafat A, Afraei S,
Abouhamzeh K, Jamee M, Al-Hussieni KJ, Mohammadi H. The effects of D-aspartate on
neurosteroids, neurosteroid receptors, and inflammatory mediators in experimental
autoimmune encephalomyelitis. Endocrine, Metabolic & Immune Disorders-Drug Targets 2.68
(Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders). 2019 May
1;19(3):316-25.

Ahmadabad HN, Abbaspour A, Panahi Y, Tahmasebi S, Hossein-Khannazer N, Afraei S,

Miladi H, Goudarzvand M, Kamali AN, Bagheri Y, Yazdani R. Anti-Inflammatory Effect of
KW-2449 on Autoimmune Encephalomyelitis: An Experimental Study on Mice. Endocrine, 2.68
Metabolic & Immune Disorders Drug Targets. 2020 Nov 5.

Kamali AN, Hamedifar H, Sepehri N, Tahmasebi S, Miladi H, Moniri S, Goudarzvand M, 0.468

6
Azizi G, Mirshafiey A. The Effect of β-d-Mannuronic Acid in Animal Model of Epilepsy.
Natural Product Communications. 2020 Apr;15(4):1934578X20920030.
Tahmasebi S, Azizi G, Miladi H, Shafiei E, Kamali AN, Hamedifar H, Fayyaz F, Rasouli SE,
Kalvandi M, Mohammadi H, Hassannia H. The Effects of G2013 (α-L-guluronic Acid) in a 2.869
Pentylenetetrazole-induced Kindling Animal Model of Epilepsy. Innovations in Clinical
Neuroscience. 2020 Apr 1;17(4-6):9.
* Journal’s impact factor (IF) in 2020 can be found on http://rsf.research.ac.ir through
the internet network of Medical Universities