the clinical trial

All of these data are now available at https://clinicaltrials.gov/ct2/show/NCT04737278.

In 2014 Mitosynergy LLC commissioned aCanadian company called KGK Synergize to conduct a randomized, double-blind, placebo controlled, parallel study.This page is essentially the results of a clinical trial of Cu(I)NA₂,referred to as Cunervmuspir on this page, for relief of fibromyalgia neuromuscular pain that shifted to the relief of any neuromuscular pain.  The results in blood work in Table 17 have been presented in a new light on external sites concerning copper in immune system regulation: general copper in the immune system,  fish data and this human study showing lyphocyte count increase and neutrophil count decease , toxic Cu-2 as it relates to Alzheimer’s Disease , niacin in the immune system These data contributed to Cu(I)NA₂, aka Cunermuspir, being awarded a “no objections 905” letter from the FDA. Only data from KGK Synergize are presented on this page.

1. The Study Participants

A total of 72 subjects were consented and screened, with 56 subjects (28 males and 28 female) being eligible to participate in the study. Fifty-six subjects with muscle/nerve pain were randomized at a ratio of 1:1 to one of two treatment groups. To evaluate primary and secondary objectives, study assessments were conducted at Baseline, and Day 28 ± 2. The primary objective of this study conducted in subjects with unresolved persistent muscle or nerve pain was to examine the effect of Cunermuspir on quality of life.

This study was reviewed by the Natural Health Products Directorate (NHPD), Health Canada and a research ethics board. Notice of authorization was granted on October 28, 2013 by the NHPD, Ottawa, Ontario and unconditional approval of the protocol amendment dated on December 12, 2013 was received on January 21, 2014 from Institution Review Board Services, Aurora, Ontario. Health Canada was notified of the protocol changes on December 16, 2013 and acknowledgement from Health Canada was received on December 24, 2013. All of the subjects signed the informed consent. All of the procedures were in accordance with the Helsinki Declaration revised in 2008.

Inclusion Criteria

1. Male or female age 18-75 years
2. If female, subject is not of child bearing potential. Defined as females who have had a hysterectomy or oophorectomy, bilateral tubal ligation or are post-menopausal (natural or surgically with > 1 year since last menstruation). OR Female subject of childbearing potential must agree to use a medically approved method of birth control and have a negative urine pregnancy test result.
3. Subject has unresolved persistent muscle or nerve pain (muscle or nerve pain population)
4. Subjects using other therapies for nerve/muscle pain (e.g., exercise, TENS, acupuncture, exercise, psychotherapy, massage, physiotherapy, etc.), must be used at a stable schedule for 1 month prior to the trial and subject agrees to continue these therapies at the same schedule during the trial avoiding changes in frequency or intensity and to record therapies in the study diary
5. Agrees to comply with study procedures
6. Has given voluntary, written, informed consent to participate in the study.

Exclusion Criteria

1. Women who are pregnant, breastfeeding, or planning to become pregnant during the course of the trial
2. Planned surgery during the course of the trial
3. Use of prescription drugs for fibromyalgia or nerve pain (e.g.Lyrica, Cymbalta and Savella and others).
4. Use of prescription medications for depression, anxiety or other mental disorders
5. Requires the use of prescription drugs to control pain (other than provided rescue medication)
6. Use of oral or topical prescription or over the counter medications or natural health products for pain relief 3 days prior to randomization and during the trial (other than provided rescue medication)
7. Use of natural health products including vitamins and minerals within 3 days prior to randomization and during the trial
8. Use of blood thinning medications (e.g. warfarin)
9. Chronic Lyme disease or chronic parasitic infections
10. Uncontrolled hypertension defined as untreated systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg
11. Subjects with diabetes
12. History of bleeding disorders, or significant blood loss in the past 3 months
13. Alcohol use >2 standard alcoholic drinks per day and/or alcohol or drug abuse within the past year
14. Allergy or sensitivity to study supplement ingredients or acetaminophen
15. Participation in a clinical research trial within 30 days prior to randomization
16. Individuals who are cognitively impaired and/or who are unable to give informed consent
17. Any other condition which in the Investigator’s opinion may adversely affect the subject’s ability to complete the study or its measures or which may pose significant risk to the subject

Forty-nine of the participants enrolled completed the study. The per-protocol population consisted of an approximately equal number of male (51%; 58% Cunermuspir, 44% placebo) and female participants (49%; 42% Cunermuspir, 56% placebo). Ninety-six percent were of non-hispanic or latino descent (76% placebo; 100% Cunermuspir), with 75% being classified as white western European (76% placebo; 67% Cunermuspir). Sixty-nine percent of participants reported occasional alcohol use at the time of enrolment (52% placebo; 48% Cunermuspir). No significant differences between the treatment groups were seen in the vital signs, biometric measures, demographics or characteristics in the protocol population

2. Safety Evaluation

Extent of exposure

This study consisted of a 28 day treatment period.

breakfast and one capsule between lunch and supper with food. 28 participants took 2 capsules of Cunermuspir (12.12 mg of copper niacin chelate). One capsule was taken each morning with breakfast and one capsule between lunch and supper with food.

2 Supplements Administered

2.1 Cunermuspir Complex

Medicinal ingredients:  Copper Niacin Chelate, 6.06 mg per capsule.  Non-medicinal ingredients: Organic evaporated cane juice powder, hypromellose, titanium dioxide

2.2 Placebo

Ingredients:  Organic evaporated cane juice powder, hypromellose, titanium dioxide

2.3 Dosage Preparation and Dosing Regimen

The investigational products were provided by the sponsor. The investigational products were carefully stored at study sites in a lockable, limited access area, accessible only to study team personnel in compliance with pertinent regulations. Only authorized persons had access to the investigational products. The products were stored at room temperature and were not exposed to direct sunlight or heat.  Participants were given 2 capsules of study product in the clinic at visit 2 (Day 0). Capsules were opened and participants asked to take the contents sublingually with a small meal. Starting on Day 1, participants were instructed to take the study product with the following directions: 1 capsule orally in the morning with breakfast, and one capsule orally between lunch and dinner, with food, for a total of 2 capsules daily. Participants were instructed to take all capsules with adequate, but not excessive, missed a dose they were instructed to take the next dose as they remembered. Participants were instructed not to exceed 2 capsules daily. Participants were also asked to consume a minimum of six

8oz glasses of water daily during the test period. The study product was taken at least two hours before or after other medications.

S2.3.1 BIOMETRICS & VITAL SIGNS

3 Results of Safety Analysis

Table S2.3.1: Vital Signs (Systolic Blood Pressure, Diastolic Blood Pressure and Heart Rate of All

No difference between the treatment groups was seen in the SBP or heart rate at the end of study visit (day 28), however a significant between group difference in the DBP was seen at day 28 (p<0.01). This difference between the groups was not considered medically significant. No within-groups changes from baseline were seen for any of the vital sign parameters following Cunermuspir or placebo supplementation.

3.2 Hematology and clinical chemistry

 The following are breakdowns of white blood cells. We have gone back to data collected by KGK Synergize and calculated our own neutrophil to lymphocyte ratios (our NLR).

Note the increase in lymphocytes and the decrease in neutrophils. KGK never took the analysis beyond this point. We have since calculated the neutrophil to lymphocyte ratio (NLR) for each participant who completed this study.

Glucose is absorbed by the proximal tubules of the kidney and may be a measure of renal function. Blood urea and creatinine as also renal markers. The estimated glomerular filtration rate (eGFR)

The next section is electrolytes that should be reabsorbed by the kidneys. According to company accounts, the participants started this study dehydrated. This was in the dead of winter in Ontario. It is often easy to become dehydrated when it is very cold.

This brings us to our next section: liver enzymes in the blood. The only reason why enzymes in hepatocytes will appear in the blood is if there were damage to the liver. Sometimes liver injury is the result of detoxifying foreign materials.

The final section, bilirubin and copper rounds up the liver function. The liver should incorporate copper from the small intestine into ceruloplasmin.

ANCOVA analyses revealed significant between group differences in red blood cell (p=0.05) and lymphocyte numbers (p<0.01) and eGFR (p=0.01), where the values were higher in the Cunermuspir group. Significant between group differences were seen for MCV (p<0.01), MCH (p<0.01), platelet (p=0.02), neutrophil count (p=0.03) and copper concentration (p=0.03) at day 28, with the values were lower in the Cunermuspir supplementation group than the placebo group. In the Cunermuspir supplementation group, there were significant within group decreases from baseline in serum potassium (p<0.001) and chloride levels (p=0.003) and an increase in GGT levels (p=0.01). A trend towards a significant 3% increase from baseline (p=0.10) in serum copper levels was also seen with Cunermuspir supplementation, however copper levels remained in the normal laboratory range for the population in this study. In contrast, the placebo group showed significant within group increases from baseline in serum neutrophil cell concentration (p=0.05) and fasting glucose (p=0.04) and decreases in sodium (p=0.01), potassium (p<0.001) and chloride levels (p=0.003). All of the mean hematology and clinical chemistry values were within the normal physiological reference range and none of the within group changes from baseline or differences between the groups were considered medically significant.

2.4 Adverse events

The most common AE reported was headaches, which occurred in 3 (2 Cunermuspir and 1
placebo group) of the 56 study participants (5%). One report of headache was classified as
possibly related to the investigational product. This study participant had received Cunermuspir.

2.4.1 Frequency of adverse events

A total of 18 AEs were reported during the course of this study, with 9 AEs being reported in each of the Cunermuspir and placebo supplementation groups. The greatest frequency of AEs was seen for gastrointestinal disorders (39%; 7 of 18 AEs; 4 in the Cunermuspir and 3 in the placebo group), followed by infections and infestations (33%; 6 of 18 AEs; 2 in Cunermuspir and 4 in placebo groups) and nervous system disorders (17%; 3 of 18 AEs; 2 in Cunermuspir and 1 in placebo groups)

Only one AE in the Cunermuspir supplementation group, headache was considered to be possibly related to the investigational product by the KGK Synergize principal investigator.