Theramine® in the Prevention of Migraine Headache

This randomized double blind placebo-controlled study will enroll approximately 80 otherwise
healthy subjects with a diagnosis of migraine headache. All subjects will be medically
stable at enrollment and be on a stabilized dosage of daily medications.

The study duration will be approximately four months and the study will be divided into 3
phases (described below). Participants will complete daily headache diaries throughout all
phases of the study, which will assess the presence or absence of headache as well as its
characteristics (e.g. unilateral vs. bilateral, worse with exertion, moderate to severe
intensity, throbbing quality, presence of associated symptoms [nausea, vomiting,
photophobia, phonophobia]. The peak severity of the headaches will also be rated on a 0-10
scale each day. The characteristics of the headaches will enable us to classify headache
days into those with migraine and non-migraine headaches. A migraine day will be considered
any day with a moderate to severe headache that has one of the following two associated
symptoms: 1) both photophobia and phonophobia or 2) nausea or vomiting. A headache day will
be defined as the presence of any headache regardless of its characteristics.

Migraine preventative medications will be permitted, but no changes in dosage will be
allowed during the four month study. Migraine abortive meds will be permitted and will be
administered per their standard routine.

Phase 1: During this phase, participants will complete daily headache diaries for 30 days,
but no study medication will be given. This phase will last approximately 1 month and will
establish a baseline for the frequency of migraine in the absence of study medication.

Phase 2: Phase 2 will last for 1 month and represents the time period of initiation of the
study medication. Participants will be randomized to either 2 capsules of Theramine® BID
(Group A) or matching placebo (Group B) in a 1:1 treatment allocation. Subjects will take
the study medications (Theramine® or placebo) for the duration of this phase and complete
daily headache diaries. Participants will also complete a Headache Impact Questionnaire
(HIT-6), which is a validated questionnaire to assess headache related disability in the
last month. This phase will not be included in the data analysis as it may take 1 month to
see a treatment effect after starting a preventative.

Phase 3: Phase 3 will last 2 months and represents the time period during which the efficacy
of Theramine® will be determined. Participants will continue to complete headache diaries
and will continue to Theramine® or placebo during this phase. They will also complete a
HIT-6 questionnaire.

There will be four study visits, which will be described below.

Office Visit 1: Following informed consent, a physical and neurological exam and vital signs
will be completed. A urine or serum pregnancy test will be collected by all female subjects
of childbearing potential. Routine labs (electrolyte panel with creatinine, liver enzyme
profile and CRP), will be collected. Eligible participants will be trained during the visit
to complete daily headache diaries. It is anticipated that this visit will last for 2 hours.

Office Visit 2: At Visit 2, research staff will review the diary information completed
during phase 1. Subjects who complete a minimum of 25 out of 30 days of their daily headache
diary will be asked to continue participation with Phase 2 of the study. They will receive
268 capsules of study medication (enough for 67 days) and will be instructed to record any
adverse events experienced from taking the study medication. During the office visit,
subjects will complete the HIT-6 questionnaire. It is anticipated that this visit will last
for 1 hour.

Office Visit 3: At Visit 3, research staff will review the diary information completed
during phase 1. Subjects who complete a minimum of 50 out of 60 days of their daily headache
diary and took 80% of their study medication will be asked to complete the last month of the
study. They will receive 134 capsules of study medication (enough for 33 days) and will be
instructed to record any adverse events experienced from taking the study medication. During
the office visit, subjects will complete the HIT-6 questionnaire. It is anticipated that
this visit will last for 1 hour.

Office Visit 4: At Visit 4, medical and medication history will be updated and adverse
events collected. A urine or serum pregnancy test will be collected by any subjects of
childbearing potential if study medication was taken and a blood test for CRP will be done.
Pregnancy testing and CRP may be completed at Visit 3 if subjects will not be returning for
a Visit 4. Study medication accountability and compliance will be assessed by counting all
the pills that had been returned by the study participant. Subjects will complete the HIT-6
questionnaire. It is anticipated that this visit will last for 1 hour.

The study coordinator will contact participants by phone, email, mail or texting at least
one time per month to schedule appointments and discuss any questions. This study is minimal
risk and subjects will not need to return study drug if they withdraw or are withdrawn by
the investigator. Information regarding study medication that is not returned for any reason
will be documented in the study medication accountability log. Lost to follow up will be
defined as any subject who has failed to contact the study coordinator after the coordinator
has made six attempts to contact the subject over a 30 day period.

The Investigator will access in a case-by-case basis should a subject request additional
days to complete the study or request replacement study medication due to loss.
Documentation of such requests and outcomes will be maintained in subject's study file.

INCLUSION CRITERIA: The inclusion criteria will be the following:

1. (male and female) 18-65 years of age

2. Women of child-bearing potential, has a negative pregnancy test (urine or serum) at
screen, and agrees to one of the following:

1. Complete abstinence from intercourse from 2 weeks prior to administration of the
investigational product, throughout the study, and for a time interval (5 days)
after completion or premature discontinuation from the study,

2. History of bilateral tubal ligation,

3. Hormonal Contraception (oral, patch, etc.) as approved by the Investigator,

4. Sterilization of male partner; or,

5. Any intrauterine device (IUD),

6. Spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or
spermicide plus a female diaphragm); or,

7. Any other barrier methods (only if used in combination with any of the above
acceptable methods);

3. Diagnosis of migraine headache (ICHD 1.1-1.5) as determined by criteria established
by the International Classification of Headache Disorder (ICHD-II).

4. 4-14 days per month with migraine averaged over past 3 months, as self reported by
subject.

5. Migraines symptoms must have been present for at least one year prior to enrollment
in the study.

6. The onset of migraine symptoms must have occurred before age 50.

7. Is medically stable as determined by the Investigator.

8. If taking any concomitant preventative medication(s), is on a stabilized dosage at
the discretion of the investigator.

9. Is willing to stay on current preventative medication(s) for the duration of the
study.

10. Is able to take oral medication, adhere to the medication regimens and perform study
procedures.

11. Is able to understand and communicate intelligibly with the study observer.

12. Is able to read and comprehend written instructions and be willing to complete all
procedures and assessments required by this protocol.

13. Is able to demonstrate the willingness to participate by signing and understanding an
informed consent after full explanation of the study.

EXCLUSION CRITERIA: The exclusion criteria will be the following:

1. Is pregnant, actively trying to become pregnant, or breast feeding.

2. A diagnosis of medication overuse headaches as determined by the investigator.

3. Chronic medical illnesses (eg. lupus, malignancy, infections, sarcoidosis) that could
potentially modulate the frequency of migraine headache.

4. Has evidence of alcohol or substance abuse within the last year or any concurrent
medical or psychiatric condition which, in the investigator's judgment, will likely
interfere with the study conduct, subject cooperation, or evaluation and
interpretation of the study results, or which otherwise contraindicates participation
in this clinical trial.

5. Chronic daily headache (≥ 15 days per month with headache of any kind) averaged over
past 3 months.

6. Abnormal creatinine, BUN, and/or Liver Function Enzymes will be assessed and
exclusion will be at the discretion of the Investigator.

7. Allergy or hypersensitivity to any ingredients in Theramine® including
arginine-containing preparations and whey protein (milk).