Regulating Urine pH Levels to Alleviate Chronic Joint Pain

STUDY SYNOPSIS / Literature Review Inflammation is a local immune response to injury,
infection and foreign molecules. Notwithstanding the provoking cause, inflammation is
thought to have evolved as an adaptive response for restoring tissue homeostasis. The local
inflammatory response causes acidosis and pain has been associated with induced acidosis of
various origins - diet, injury, exercise, stress, medications, disease state or aging.

Inflammatory and degenerative joint diseases are major causes of chronic pain. In general,
inflammatory causes (e.g. rheumatoid arthritis, RA) are more common in younger individuals,
while degenerative causes (e.g. osteoarthritis, OA) are more often seen in the elderly
[Schaible et al, 2009]. Pain perception is extremely complex and a perceived connection has
been noted between the level of pain felt by individuals and bodily fluid hydrogen ion
concentration, i.e. pH; oral water-soluble alkaline components containing K, Ca, Mg and Cl
salts have been used for reducing bodily fluid and tissue acid concentrations. Urine pH is
now considered to reflect the bodily acid-base balance and is directly related to the
dietary acid-base load [Welch et al, 2008].

Currently, potassium citrate (Kcit, 45-60 mEq daily) has been widely used in urology for
treatment of patients with uric acid and cystine stones [Sterrett et al, 2008; Spivacow et
al, 2010]. Aside from the use of Kcit in the treatment of kidney stones, there have been
isolated reports about the anti-inflammatory and hypoalgesic systems effects of Kcit.
Alkalinization by diet alone has also been effective for removing uric acid from the body,
though its effects on urine pH levels are weaker [Kanbara, Hakoda & Seyama, 2010]. It is
considered that alkalinization of urine reflects body fluid alkalinization. This has the
perceived effects of increased bone density, improved muscle function, and a speculative
decrease in insulin resistance [Pizzorno, Frassetto & Katzinger, 2010].

Research Project Question/Theme The investigators aim to determine causal relationship
between regulating urine pH levels between 7.0 and 7.5 and decreasing chronic joint pain.
The investigators hypothesize that maintenance of an alkaline urinary pH will result in a
decrease in personally reported levels of chronic joint pain using a citrate treatment
regimen.

Project Design:

Subjects will be recruited from local physician's practices, primarily at TTUHSC clinics, by
the Principal Investigator and the Co-Investigators. Subjects who report a presence of joint
pain for more than six months, and meet the inclusion/exclusion criteria, will be eligible
for participation.

Any Adverse Events (AEs) will be monitored by the Principal Investigator and
Co-Investigators, and reported by the Study Coordinator to the IRB.

Subjects for the study will be identified by the Principal Investigator and Co-Investigators
from local TTUHSC clinics.

After the subject agrees to participate and informed consent has been given, the study
coordinator will explain the study procedures and baseline measurements will be assessed
using diagnostic imaging and lab testing. All subjects will be asked to obtain and/or
provide a copy of recent X-rays or an MRI of the affected joint and lab tests (CBC, liver
and kidney panels). Images and tests must be recent and taken within the past 6 months of
enrollment in the study.

After the baseline measurements have been established, instructions on the urine
alkalinization treatment regimen will be distributed to the subject and treatment solution
will be obtained. This treatment will vary from person to person and is easily modified.

Subjects will measure, report, and take the treatment for 6 months.

While on the treatment, all subjects will be asked to report and/or measure the following
values on a daily basis:

- Report when and how much treatment was taken that day

- Measure urine pH levels daily at 10 A.M. using a pH strip

- Rate their pain 3X daily using a modified pain rating scale

- Report daily food and beverage intake

- Visit the physician investigator for monthly a follow-up visit to review the pain
ratings and pH values noted during the past month

Analysis:

Using the SAS System, the investigators calculated the minimum number of enrolled subjects
that is required to achieve statistical results is 21. The investigators estimated that a
minimum number of 16 subjects must complete the study in order to achieve sufficient,
statistically powerful results. In order to ensure successful completion of the statistical
data analysis, the investigators decided to enroll twice the minimum number of subjects
required (16x2) and will enroll a total of 32 subjects.

Inclusion Criteria:

1. Presence of joint pain of perceived inflammatory and non-inflammatory origin for more
than six months. More specifically:

- Subjects with osteoarthritis (OA) of the knee will be preferred for inclusion in
this study.

- Subjects with other joint pain history will be included pursuant on approval
from Dr. Miller or Dr. Pema.

2. Age 21 to 80 years old and otherwise in good health (excluding the joint pain).

3. Able to understand and comply with the assigned urine alkalinization instructions.

4. Has a working and reliable telephone number for continued contact as necessary during
the study.

5. Ability to obtain X-rays of the affected joint. Imaging of the painful joint will be
necessary at the beginning of the study for baseline considerations; if images from
the last 6 months are available, no new imaging would be necessary.

6. Ability to obtain lab tests (Complete Blood Count and Comprehensive Metabolic Panel)
or can obtain documentation of recent lab tests that have been taken within one month
prior to enrollment.

7. Ability to obtain lab tests at 3 and 6 months during participation in the study.

Exclusion Criteria:

1. Presence of joint pain with known joint osseous changes.

2. Pregnant or lactating women will not be enrolled in the study.

3. Positive medical history of:

- Diabetes

- Neuropathies

- Gout

- Psychiatric diseases and conditions, including anxiety, depression, PTSD,
distress

- Psychosocial abnormalities

- Dementia or other memory disturbances

- Alcoholism or substance abuse

- Renal failure and/or abnormal renal function (kidney disease or dysfunction).
Specifically, Creatinine (Creat) values that are over 1.2mg/dL and Urea Nitrogen
(BUN) values that are over 22mg/dL are considered abnormal.

- No history of cardiovascular disease, intestinal angina or arrhythmias

- No history of sodium restrictions

- Pt. should not be taking medications which produce pain such as angiotensin
converting enzyme (ACE) inhibitors and Statins (Lisinopril, Quinapril, Ramipril)

4. Does not have reliable telephone communication.

5. Does not have the ability to obtain an X-ray and does not have the ability to obtain
documentation of a recent X-ray within the last six months.

6. Does not have the ability to obtain lab tests (Complete Blood Count and Comprehensive
Metabolic Panel) and does not have the ability to obtain documentation of recent lab
tests that have been taken within one month prior to enrollment.

7. Does not have the ability to obtain lab tests at 3 and 6 months during participation
in the study.