This will be a six-week, randomized, parallel, two group, open-label design. Patientswill be treated with Paragon Novel Metabolic Regulator (PNMR) + standard of care (SOC) orSOC alone for 6 weeks for the treatment of Long COVID. All patients will also be providedwith with Dietary & Lifestyle recommendations specifically designed to enhance immunesystem function and reduce viral proliferation.Patients will be assessed in the clinic at screening/baseline, 3 and 6 weeks while ontreatment, and by telephone at 4 weeks post-treatment.All patients will be asked to fill in a diary to record their daily treatment dosage whenbeing treated with PNMR + SOC or with SOC alone. Primary objective: To evaluate theefficacy of PNMR + (SOC) vs. SOC in the treatment and management of patients with longCOVID.
Because:
- A) ~ 55% of patients have healed from long COVID, but have only been cured via a
gradual, natural restoration of that patient's previously depleted endogenous
mitochondrial and immune system function, and that
- B) a fully-functioning immune system comprises the only known comprehensive system
of cellular-driven mechanisms which make it capable of: neutralizing almost any
pathogen(s); metabolizing and clearing systemic necrotic and fibrotic tissues
occurring from injury; then healing those tissues and organs; and restoring normal
signaling within the body's cells; to reverse as many as 300 different chronic
symptoms that can affect a patient with long COVID,
And because metabolic research shows:
- that long COVID patients are depleted of key nutrient metabolites enabling immune
system and mitochondrial function, thereby making them unable to mount a properly
regulated immune response,
- and that COVID-19 and long COVID patients are depleted of specific amino acids and
other metabolites compared to those fully recovered from COVID-19, whose metabolite
levels have recovered to normal levels,
- therefore: without the necessary balance of metabolites to rapidly and fully
activate that patient's mitochondrial and immune system metabolism, many COVID-19
and long COVID patients cannot fully recover.
- Further metabolic research also shows:
- human cell systems maintain significant cellular storage levels of a wide range of
essential nutrient metabolites supporting enzymes driving mitochondrial and immune
system function and healing, all of which can be depleted by serious illness, and/or
excessive exposure to any other toxic pathogens (whether industrial or environmental
contaminants, pesticides, excess exposure to blue light, other harmful radiation,
alcohol, drugs, certain Rx, lack of sleep, exercise stress, work stress, processed
foods, refined sugars, nutritional imbalances, malnutrition, etc., and/or any
combinations of the above), and that,
- Affected cell systems and components (including the cytosol, mitochondria,
associated metabolic pathways within cells, the lymphatic system, white blood cells,
antibodies, antimicrobial peptides, defensins, and other compounds) require specific
concentrations and ratios of specific amino and fatty acids - and corresponding
concentrations and ratios of a wide range of specific metabolites - that together
enable their continuous enzyme-driven metabolism within those cell systems.
- This is possible because those enzyme systems are operating at speeds up to a
million X faster than typical random chemical reaction. Further, the 1500-4000
interdependent enzymes found within each cell type all work together to supply
byproduct from one enzyme reaction as input substrate to another in high-speed
harmony to drive the metabolism of each cell type.
- Therefore, anything disrupting the inflow of enzyme activators or substrates
necessarily negatively impacts the flow of enzyme chemical byproduct output, and can
seriously disrupt or dysregulate the entire enzyme matrix within the cell, and
various organs, tissues and/or other physiological systems affected.
- And therefore, when the body is subjected to excess pathogenic microbes or any other
type of toxin listed above, the body's mitochondria and immune system cells have to
work longer and harder to neutralize pathogens, detoxify and rebuild tissues,
- and therefore, to maintain homeostasis, the body must consume higher levels of
essential nutrient metabolites and other co-enzyme factors supporting this critical
enzyme activity. If any of the essential nutrient metabolites supporting that enzyme
activity is deficient or depleted, the proteome (net sum of enzymes in the body)
supporting mitochondrial and immune system function can be significantly and
negatively impacted.
- Therefore: the PNMR was specifically designed to replenish those intracellular
reserves of nutrient metabolites supporting this comprehensive endogenous
mitochondrial and immune system function described above:
- The PNMR capsules (provided in 1 - 6 packets per day, based on a patient's
individual deficiency symptoms and needs) are designed to quickly restore optimum
and balanced intracellular storage levels of those essential metabolites driving the
balanced intracellular enzyme activity and metabolism required to maintain
mitochondrial and immune system function, healing, and homeostatic regulation.
- Further, this specific trial design is somewhat unusual - and is necessary - because
there has never been a disease in modern human history like long COVID:
- which is continuing to have unprecedented detrimental effects on human health and
all national economies around the world,
- is being driven by variants at least 12 X more infectious than the original Wuhan
virus,
- which results in viral persistence within tissues in those with even mild long
COVID, which continues to mutate new COVID-19 variants in the entire global
population with long COVID (and those with acute COVID-19), with the mutation rate
measured to be ~ 1 mutation every 5 days in one long COVID patient in isolation in
Germany,
- with research showing repeat COVID-19 infections increase the probability of
developing long COVID,
- which is causing long COVID to spread quickly to all parts of the world, and is now
estimated to have affected as many as 36% of all people who have had COVID-19, with
just under half who contracted it who are not healing.
- with no simple, approved testing method to quickly diagnose long COVID,
- and based on Nov 2024 research from Harvard/Mass General Brigham (which used AI to
help identify signs of long COVID, track symptom manifestation over time, and
eliminate alternative explanations for 300,000 patients' symptoms) the data suggests
that 22.8% of that population experience long COVID symptoms, a figure that may
paint a more realistic picture of the pandemic's long-term toll and global reach.
- And as most patients infected with long COVID globally have milder symptoms, and are
not aware of their infection and its potential to cause serious clotting disorders,
as well as other serious complications, or that they are actively mutating new
COVID-19 variants - some which may mutate to a COVID-19 variant of concern (VOC) via
convergent evolution,
- and therefore, if the PNMR is proven to be successful reversing long COVID disease,
as well as the mutation of new COVID variant mutations within such long COVID
patients,
- and therefore, if the world's goal is to reduce the current global levels of
COVID-19 VOC transmission - then it's estimated that 75-85% of the 20-35% of the
global population with long COVID will need to receive the PNMR treatment, to
achieve the global herd immunity necessary to finally eradicate 75-85% of long COVID
globally, which would thereby eradicate the vast majority of the rampant current
mutation and transmission of new COVID-19 VOC from within long COVID patients
globally, and thereby, very dramatically reduce global COVID-19 VOC transmission.
When 75% - 85% of the world's population are immune to COVID viral infection, it may
be possible to finally eradicate the transmission of COVID-19 virus, and ultimately
eradicate the COVID-19 strains of virus.
- Therefore, the critical importance of all factors above makes it equally important
to design a PNMR Phase II trial that:
- 1) clearly demonstrates the PNMR is essential to a rapid cure of chronic, systemic
long COVID disease and tissue damage,
- 2) while also demonstrating the combination of confounding dietary & lifestyle
factors that enable an even more rapid reversal - to demonstrate to the world the
most effective use of this new class of medicine to most rapidly reverse disease.
This is why the Dietary and Lifestyle Recommendations, which have been demonstrated by
peer-reviewed research to benefit those with chronic viral infections causing
mitochondrial & immune system dysfunction, are being provided to both the control &
treatment groups in the trial. This gives both patient groups in the trial potential
mechanisms for healing.
And while initial medical case studies indicate the ingredients in the PNMR potentially
represent a powerful curative treatment for the chronic tissue & organ damage many long
COVID patients have, effective dietary & lifestyle measures are critical to further
accelerating this healing process.
- Further, because there is no treatment yet approved for long COVID, there is no
approved standard of care (SOC) for long COVID:
- therefore, the trial's design, and patient evaluations performed at Day 0 upon
screening, Day 21 (end of week 3) midway through treatment, and at Day 42 (end of
week 6) upon termination of treatment, allow the evaluation of 3 distinct levels of
treatment on a long COVID patient's physical and mental function:
- A) SOC (no treatment) prior to the trial: On Day 0, upon screening, up to 82
patients who've not received any long COVID treatment will be evaluated,
establishing a baseline for patients without treatment,
- Then upon evaluation, those up to 82 patients will then be randomly split into 2
groups:
- B) Group 1 of up to 41 patients will receive PNMR treatment + SOC + Dietary &
Lifestyle Recommendations and be evaluated at the end of 3 & 6 weeks, establishing
potential for improvement with PNMR + Dietary and Lifestyle Recommendations,
- C) Group 2 of up to 41 patients will receive SOC + Dietary & Lifestyle
Recommendations and be evaluated at 3 & 6 weeks, establishing potential for
improvement with Dietary & Lifestyle Recommendations alone.
- Therefore, this trial design will evaluate whether:
- the group receiving the Dietary and Lifestyle Recommendations alone sees some
improvement over no treatment, or SOC alone,
- the group receiving the PNMR + the Dietary and Lifestyle Recommendations sees an
even greater improvement over no treatment, or SOC alone.
Drug: Paragon Novel Metabolic Regulator (PNMR)
Research shows human cell systems maintain significant cellular storage levels of a wide
range of critical metabolites supporting enzymes driving mitochondrial and immune system
function and healing, all of which can be depleted by serious illness. Such cell systems
and components (including the cytosol, mitochondria, metabolic pathways within cells,
white blood cells, antibodies, antimicrobial peptides, enzymes, and other compounds)
require specific concentrations of specific amino and fatty acids - and corresponding
concentrations of a wide range of specific metabolites - that together enable their
continuous metabolism within those cell systems. The PNMR capsules (provided in 1 - 6
packets per day) are designed to quickly restore optimum and balanced cellular storage
levels of those critical metabolites driving the balanced intracellular enzyme activity
and metabolism required to maintain mitochondrial and immune system function, healing,
and homeostatic regulation.
Other: Dietary and Lifestyle Recommendations
Dietary and Lifestyle Recommendations specifically designed to enhance immune system
function and reduce viral proliferation
Inclusion Criteria: The patient must meet all the following criteria to be enrolled in
the study:
1. ≥19 years of age.
2. Negative COVID-19 test for a minimum of four (4) weeks prior to enrollment in the
study.
3. Confirmed COVID-19 diagnosis by Polymerase chain reaction (PCR) test, antibody test,
or clinical diagnosis more than four (4) weeks prior to enrollment in the study.
4. Long COVID diagnosis according to the WHO criteria, specifically the continuation or
development of new symptoms three months after the initial SARS-COV-2 infection,
with these symptoms lasting for more than two months with no other explanation.
5. For women of childbearing potential involved in any sexual intercourse that could
lead to pregnancy: Negative pregnancy test and willingness to use contraceptive
(consistent with local regulations) during the study period. Approved contraceptive
methods include contraceptive pills or patches, hormonal implants, intrauterine
device (IUD), diaphragm or cervical cap with spermicide, and condos with spermicide.
Note: If participant become pregnant during the study, they must stop taking the
study products immediately and inform the study investigator.
6. Patient agrees to stop taking any over the counter supplements, vitamins, or natural
products as well as any of the prohibited medications during the study.
7. Patient agrees not to use medications affecting directly (or potentially) the
objectives of the study such as fatigue and cognitive function during the study.
8. Willing to adhere to the study diet and exercise recommendations to the best of the
patient's ability.
9. Willing to complete the 6MWT.
10. Willing to complete the patient self-administered questionnaires and diaries.
11. Signed informed consent form by any patient capable of giving consent, or, when the
patient is not capable of giving consent, by his or her legal/authorized
representatives.
Exclusion Criteria:
1. Subject is a female who is breastfeeding or pregnant or trying to conceive.
2. Subject with a vegetarian diet or not able to follow the dietary guidelines.
3. Known hypersensitivity to PNMR or its ingredients.
4. Participating in other drug clinical trials (participation in COVID-19 antiviral
trials may be permitted if approved by sponsor).
5. Any condition that in the opinion of the investigator participation in the trial
increases the risk to the patient.
6. 4 weeks or more of consecutive daily supplement use of 5000 IUs Vitamin D / day
and/or 50mg Zinc (without copper) / day within 4 weeks of Day 0.
7. Use of any medications or treatments for which treatment with PNMR is
counter-indicated.
8. Subject is not able to swallow a larger number of capsules.
9. Any condition that in the opinion of the investigator would confound the study
results or would prevent the patient to complete the study.
10. Any patient for whom vitamin D3 (cholecalciferol) is contraindicated per the
following patient situations:
1. Hypersensitivity to vitamin D, any of its analogues and derivatives or to any
ingredient in the formulation
2. Hypercalcemia and/or hypercalciuria
3. Nephrolithiasis (renal calculi)
4. Severe renal impairment (eGFR <30)
5. Malabsorption syndrome
6. Abnormal sensitivity to the toxic effects of vitamin D
7. Sarcoidosis
8. Hypervitaminosis D
Cardio Health
Brampton, Ontario, Canada
Cardio Health
London, Ontario, Canada
Cardio Health
Mississauga, Ontario, Canada
Cardio Health
North York, Ontario, Canada
Samuel H. O. Bock / CSO, BA Environmental Science
514 998-3935
sbock@paragonsciences.com
John S Sampalis, PHD Epidemiology
514 934-6116
jsampalis@jssresearch.com
Sam Bock, BA Environmental Science, Study Director
ParagonClinicals Inc CEO / CSO