Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05417997 |
| Other study ID # |
APRON 2020-OK-01 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
May 29, 2021 |
| Est. completion date |
December 2, 2021 |
Study information
| Verified date |
May 2022 |
| Source |
RAAS Nutritionals, LLC |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The primary objective of this study is to determine the safety and efficacy profile of the
food supplement (KUNAMIN®) containing grape juice, seed, stem, and bark given to patients
treated with the established treatment regimen against novel coronavirus infectious disease
(COVID-19) via comparing Kunamin® group versus control group in a clinical trial.
In this study, both the therapeutic effect and the safety of the Kunamin® product has been
evaluated. The study has been conducted on COVID-19 infected patients. Within the scope of
the study, Covid-19 patients consisting of male and female patients are examined to evaluate
the therapeutic effect.
COVID-19 infected patients are divided into 2 groups and the treatment group received grape
food supplements for 15 days in addition to their standard treatment. The other group
received only standard therapy. The effects of supplements containing grape products on the
COVID-19 infection process of patients are investigated, as indicated in the primary,
secondary, and tertiary endpoints. For this purpose, both the observation of routine
examination findings and the effectiveness of food supplements on viral load and antibody
levels are investigated. In the follow-up that continues for 30 days, COVID-19 Rapid Antigen
test made in USA approved by FDA is used to monitor the efficacy of Kunamin® as patient
treated by Kunamin® viral load is diminished either after 5 days, 10 days or 15 days,
COVID-19 Rapid Antibody test made in USA approved by FDA has been used to monitor the
development of IgM and IgG antibodies on day 0, day 5th, day 10th, day 15th and day 30th in
addition to PCR test of Perkinelmer by Kayseri hospital. In conjunction, the sponsor used AIT
Laboratories A HealthTrackRx Company PCR test CLIA and FDA approved for not only COVID-19 but
also 27 kinds of cold and flu viruses and 90 different kinds of bacteria.
The number of patients planned for randomization was 240, however due to dropouts the
hospital was able to screen 132 patients. Out of 132 patients we were able to enroll
randomized total of 71 patients, 47 patients in the research arm and 24 in the control arm.
Description:
We conducted a medical observation from December 2019 when there were no cases and no deaths
in America, and just the revelation of this new disease in China. There is still no cure for
COVID-19, a very contagious disease that has a tendency to destroy the immune system and has
caused many mysterious complications while vaccination is a long-term strategy.
The complete study involved 100 outpatients from January 2020 to February 2021 who attended
our clinic with flu, cold and respiratory symptoms, studied with a panel of 27 viruses and 90
bacteria which has been considered as phase 1 and phase 2 clinical trial for Kunamin® in the
United States of America.
The sponsor also contracted with CRO APRON in Turkey to conduct the third phase clinical
trial for Kunamin® for COVID-19 inpatients in Kayseri City Hospital. The number of patients
planned for randomization was 240, however due to dropouts, we were able to screen 132
patients. Out of these 132 patients, we enrolled a total of 71 patients and randomized 47
patients in the research arm and 24 in the control arm.
The median age for COVID-19 positive patients is 39.6 years old (range of 18-64 years). Forty
(56%) are female and 31 (44%) are male. The demographics include all Caucasians.
3 (4%) out of 71 patients after 40 capsules of Kunamin® were admitted into ICU and intubated,
100% survived.
Nineteen (40%) of our patients in the Turkey study had adverse events. Only one patient who
completed the 30-day trial experienced an adverse event. 17 volunteers left the trial by
their own will because of gastrointestinal tract related adverse events. All the vital signs
were in normal ranges in control and treatment group. No serious adverse events or fatality
occurred during the trial. We think the problem with the gastrointestinal tract related
adverse events is not caused by Kunamin, but by the standard treatment including at least 6
drugs. In USA our medical observation for 100 patients we used only Kunamin and we found only
two minor gastrointestinal tract related adverse events (2%), including one overdose of
Kunamin in one patient, and the use of antibiotics in another. According to FDA rules and
regulations, it is not allowed to mix a botanical drug with a chemical drug, therefore we
should never use Kunamin together with standard treatment which consisted of several drugs.
The Ministry of Health in Turkey for safety of COVID-19 patients required that Kunamin should
be used along with hospital's standard treatment.
Thanks to grape, rice, soy and edamame which contain polyphenols, resveratrol, isoflavones,
genistein are the complex of the protein that contain "KH Good Healthy" cells. US patent
10,195,243 B2, EP patent 3 148 574 B1 and US patent 10,335,446 B2.
We suggest that the mechanism of these complex compounds of natural "KH Good Healthy"
proteins which contain good healthy cells which are absorbed into the blood stream to send
signal to the body to produce new cells that are healthy. It also sends the RNA signal to the
DAMAGED, SICK, AND BAD CELLS that triggers that synthesis of good proteins that transform
these cells to become GOOD healthy cells. "KH Good Healthy" proteins also send the RNA signal
to the other currently undamaged cells to synthesize good proteins to protect them from being
DAMAGED, INFECTED and PRONE to DNA and other cellular alterations.
Besides the above-mentioned mechanism, which we believe are the most important, a secondary
or contributing mechanism is the effects of polyphenols, an important component of the grape
which contribute to produce "KH Good Healthy" cells. Finally, resveratrol may also be
involved, as we know that resveratrol is a naturally occurring stilbenoid derivative found in
plants and fruits such as grapes (Vitis vinifera). Resveratrol exhibits potent inhibition
against MERS-CoV in vitro and also significantly reduced viral-induced cell death. It is
likely that its anti-CoV activity is a result of either activation of cellular survival
factors and DNA repair in response to DNA damage via activation of the ERK1/2 signaling
pathway or prevention of virus-induced apoptosis via down-regulation of FGF-2 signaling.
RAAS products derive from soy, grapes and rice that contain high concentrations of Apo-A1,
Immunoglobulin and Albumin-like proteins. Unlike traditional human plasma derived therapies
that limit the product to one single protein, RAAS Nutritionals supplements contain up to
5,055 proteins.
APOA-1 includes HDL, which is a very important protein for a human being. The next important
proteins are immunoglobulin and albumin.
RAAS Nutritionals supplements (KUNAMIN®, KHJ®, KHJ-R™ and KUNAKINMIN®) contain up to 5,055
proteins which include 1,299 proteins (of which 959 are newly found proteins found in grapes
(Vitis vinifera), 358 proteins (of which 125 are newly found proteins in soybean (Glycine
max), 1,223 total proteins (of which 843 are newly found proteins in edamame (Glycine max)
and 2,175 proteins (of which 569 are newly found proteins in rice (Oryza sativa).
We have performed an in vitro study by using SDS page to detect the molecular weight of the
three main proteins in grape, edamame, soy and rice products that we are looking for: HDL
(High Density Lipoprotein) or APOA-1, Immunoglobulin and Albumin.
The in vitro study has shown that these products cover all from the highest molecular weight
to the lowest of the protein marker. This proves our analysis of a combination of weight in
an SDS page marker.
We used the standard of Human APOA1 lays between 35.0 kDa and 25.0 kDA. Grape, soy and rice
APOA1 spreads from 66.2 kDa down to 14.4 kDa, that means all these proteins can be found by
SDS page.
Human Immunoglobulin from plasma lays starting at 45.0 kDa and spread down 25.0 kDa. Grape,
soy and rice APOA1 spreads from 45.0 kDa down to 14.4 kDa, that means all these proteins can
be found by SDS page.
Human albumin which lays between 66.2 kDA and 45.0 kDA. Grape, soy and rice APOA1 spread from
66.2 kDa down to 14.4 kDa, that means all these proteins can be found by SDS page.
For albumin, in addition to the SDS page we used the serum protein electrophoresis that
showed the high content of alpha-1, alpha-2 beta and specially gamma (which is
immunoglobulin).
For COVID-19 we have no invitro model, therefore we used H1N1 and H3N2 models to evaluate in
vitro inhibitory activity of the 24 RAAS Nutritionals test articles against a panel of
viruses.
Activity of the articles against IFV. The activity and cytotoxicity results in the influenza
virus tests are summarized in Table 5. VX-787 was used as a reference compound. Dose response
curves of the test articles in antiviral and cytotoxicity tests. VX-787 showed the expected
activities in the tests.
KH 028, Kunamin, KH 024 and KH 019 showed inhibitory activities against influenza H1N1 with
EC50 values between 0.028% and 0.092%. KHMC, KunaFlow, KH 029, KH 021 and KHEGW had EC50
values against influenza H1N1 between 0.146% and 0.985%. Kunaking and KHEGY had EC50 values
against influenza H1N1 of 1.112% and 2.685%, respectively.
KH 019, KH 028, KH 029, KH 024, Kunamin and KHMC showed inhibitory activities against
influenza H3N2 with EC50 values between 0.014% and 0.084%. KunaFlow, Kunaking, KH 021, KHEGW
and KHEGY had EC50 values against influenza H3N2 between 0.202% and 1.831%.
For COVID-19 we have no animal model, therefore we used H1N1 model. For in-vivo model we used
H1N1 infected mouse model. We have found that APOA-1 from human plasma can prevent and treat
H1N1 virus. In our study performed at Wuxi Pharma, one of the top ten CRO's in the world, we
found that RAAS-2 (APOA-1) can prevent 100% of the Bird Flu Epidemiology in Mice.
Impressively one-week preventive treatment with 0.2 ml/0.4 ml/mouse iv/ip QD of RAAS-2
(APOA-1) totally protected H1N1-challenged mice from death and body weight loss till the end
of this study. The protection of body weight loss by the preventive treatment of RAAS-2
(APOA-1) is even better than that by oseltamivir treatment. However, the therapeutic
treatment with 0.2 ml/0.4 ml iv/ip QD of RAAS-2 only protected one mouse out of 5 mice in the
group from death and partial body weight loss of all 5 mice days 2 to 5 post H1N1 infection.
Other 4 mice in this group died days 4 to 6 post H1N1 infection. In addition, some of the
mice in the RAAS-2 therapeutic group (G2) had haematuria day 5 post H1N1 challenge and
afterward, indicating that the dose used in this group was beyond mouse tolerance in H1N1
challenge status.
B cells and T cells are the KH good healthy cells to fight back any virus and its mutations
just like Omicron. In our in vitro and in vivo studies, we have found that human APOA1 or
grape and rice APOA1 will have the ability to fight back lung cancer as well as other kinds
of cancers.
We conducted a study at WuXi App Tec titled, Characterization of lymphoid tissues and
peripheral blood in nude mouse treated with and without AFCC (Anti Fear of Cancer Cells, a
combination of 27 KH human proteins) After whole blood withdrawal, distinct cell lineage was
differentiated by cell surface marker proteins. T cells, B cells, activated B cells, mDC,
pDC, granulocytes, and monocytes/macrophages were characterized.
AFCC treatment didn't affect CD3+T cell population compared with that in nude mouse with
tumor and without tumor. After AFCC treatment, B cell population, on the other hand,
increased to the similar percentage as seen in nude mouse no tumor and nude naïve ID: APRON
2020-OK-01 Effect of Kunamin in SARS-CoV-2 RT-PCR Positive Covid-19 Patients [NCT ID not yet
assigned] increased with AFCC treatment. Macrophages and granulocytes decreased after AFCC
treatment compared with those in nude mouse with tumor. Nude mouse no tumor and nude mouse
with AFCC treatment had similar mDC and pDC percentage.
Conclusion: The effect of AFCC on curing tumor through characterizing different cell lineage
in lymphoid tissues and peripheral blood in nude mouse was investigated using staining with
different marker proteins for distinct cell lineages followed by FACS. T cells, B cells,
activated B cells, mDC, pDC, granulocytes, and monocytes/macrophages were characterized in 6
mice.
FACS analysis showed that AFCC treatment had the effect on the population of major cell
lineages in immune system. Increased CD3+T cell population was found in nude mouse treated
with AFCC compared with that in nude mouse with tumor in spleen and lymph nodes. B cells
including activated B cells also increased compared with that in nude mice with tumor in
spleen, lymph nodes, and peripheral blood. Granulocytes and macrophages, however, were found
to decrease after AFCC treatment in peripheral blood and spleen. Taken together, this study
suggests the effect of AFCC on curing tumor through changing the population of major cell
lineages in immune system, including spleen, lymph nodes and peripheral blood.
We conducted a study at WuXi App Tec titled, Characterization of draining lymph nodes and
peripheral blood in DIO mice treated with KHJ, KH103 and KHGD (KHJ is a grape product, KH103
is a soy product and KHGD Kieu Hoang Gold label) Results summary, the effects of KHJ, KH103
and KHGD on different cell lineages in lymphoid tissues and peripheral blood in DIO mice were
investigated by FACS analysis. T cells, B cells, dendritic cells, MDSCs, granulocytes and
macrophages were analyzed. Overall, KH103, KHJ and KHGD treatments showed few effects on T
cell lineages, macrophages and granulocytes but reduced the percents of B cells in both
peripheral blood and draining lymph nodes. They also elevated the percentages of pDCs in
blood and reduced the percentages of mDCs in draining lymph nodes. The causes of the
alterations remain to be further investigated.
