NEM® Versus Placebo in Exercised-induced Joint Pain, Stiffness, & Cartilage Turnover in Healthy Men & Women

Moderate exercise can induce discomfort in joints when done infrequently or when done too
intensely or for too long a period. This discomfort is often realized as either pain or
stiffness in the joint that was the focus of the exercise. For example, one's knees will hurt
after jogging for several miles, particularly if jogging for the first time. This study is
intended to evaluate whether NEM® brand eggshell membrane can alleviate joint pain or
stiffness, either directly following exercise or 12 hours post-exercise versus placebo. The
study will also evaluate NEM's effect, on cartilage turnover via the cartilage degradation
biomarker c-terminal cross-linked telopeptide of type II collagen (CTX-II). Participants will
perform a minimum of 40 steps per leg utilizing an aerobics step at the clinical site. They
will follow this exercise regimen on alternating days for 2 consecutive weeks. Changes in
pain & stiffness (immediate & 12-hour) will be compared to both baseline and to the placebo
group. Urine samples will also be collected at baseline and at the end of Week 1 & Week 2.
The change in CTX-II from baseline will be compared to the placebo group.

Inclusion Criteria:

1. Male or Female subjects must be 40-75 years of age at the time of Screening.

2. Subjects must not have been diagnosed with a JCT disease (i.e. osteoarthritis,
rheumatoid arthritis, spondyloarthritis, bursitis, gout, systemic lupus erythematosus,
fibromyalgia, etc.) affecting the hip, knee, or ankle by a licensed physician prior to
enrollment evaluation / screening.

3. Subjects must have a resting pain/discomfort score of ≤ 2 on the 10-point continuous
scale in the knee with the most severe pain/discomfort at the Follow-Up
Screening/Baseline (first exercise visit).

4. Subjects must be willing and healthy enough, as judged by the clinical Investigator or
Sub-Investigator(s), to perform moderate exercise.

5. Subjects must be available for and willing to attend all evaluation visits.

6. Subjects must be able and willing to give informed consent.

7. Subjects must be willing to use only acetaminophen as rescue pain medication, if
needed.

8. Subjects participating in prior studies evaluating eggshell membrane, curcumin, fish
oil or collagen can participate in the present study so long as they are not currently
taking an eggshell membrane, fish oil, curcumin, or collagen supplement and have not
done so for 60 days prior to screening.

Exclusion Criteria:

1. Subject is currently receiving therapy with remission-inducing drugs (i.e.
methotrexate, TNF biologics, etc.), immunosuppressive drugs (i.e. corticosteroids,
transplantation medications, etc.) or planning to use these products during the study
period.

2. Subject has been diagnosed with any clinically significant confounding inflammatory
disease or condition that would interfere with the study evaluation, as judged by the
clinical investigator (i.e. pseudo gout, Paget's disease, chronic pain syndrome,
active rheumatic fever, etc.).

3. Subject has known allergy to any of the investigational products, including but not
limited to eggs or egg products and rice or rice flour. If any subject becomes
sensitive during the study, they will immediately be excluded from continuing in the
study.

4. Subject suffers from clinically significant cardiac, pulmonary, or other complications
that would prevent them from performing moderate exercise or could pose a risk to the
subject's health, as judged by the clinical investigator.

5. Subject participates in activities involving intensive use of the lower extremities
(i.e. running / jogging, sports, bicycling, dancing, etc.) 2 or more days per week or
participates in activities that involve moderate use of the lower extremities (i.e.
walking, golfing, yoga, etc.) 3 or more days per week.

6. Subject's body weight is greater than 300 pounds (136.1 kg) at the time of Screening.

7. Subject is currently taking or is unwilling to forgo the use of prescription,
over-the-counter (OTC) treatments, and/or dietary supplements affecting joint health
within 30 days prior to baseline evaluation and for the duration of the study.
Prohibited medications include: NSAIDs, analgesics (other than acetaminophen),
opioids, anti-depressants (of all drug classes for this indication, including but not
limited to SSRI's such as citalopram and fluoxetine, TCA's such as amitriptyline and
amoxapine, SNRI's such as duloxetine or SNRI's used for fibromyalgia such as
milnacipran and NDRI's such as bupropion), other medications for the management of
painful conditions (i.e. fibromyalgia) including gabapentin and tizanidine & joint
supplements. Examples of these types of medications are: aspirin, ibuprofen, naproxen,
oxycodone, propoxyphene, diclofenac, celecoxib, amitriptyline, duloxetine,
glucosamine, chondroitin, MSM, white willow bark, turmeric or curcumin, Boswellia,
fish oil, etc.

a. Washout Periods: Subjects are eligible to participate in the study following a
7-day washout period for opioids, a 14-day washout period for analgesics & NSAIDs, and
a 90-day washout period for steroids, anti-depressants, or JCT dietary supplements
(i.e. glucosamine, chondroitin, MSM, etc.) Acetaminophen must not have been taken
within 24 hours of the first baseline evaluation.

8. Subject is involved in any other research study involving an investigational product
(drug, device or biologic) or a new application of an approved product, within 30 days
of the first baseline evaluation.

9. Pregnant and breastfeeding women, or women who intend to become pregnant during the
course of the study.

10. Subject has a history or positive test result of HIV, hepatitis B or hepatitis C.