Urinary Excretion of Acetylamantadine by Normal Healthy Volunteers
Condition: Healthy Metabolism
Study type: Interventional

Summary: 
      Amantadine appears to be a specific substrate for acetylation by spermidine/spermine
      N1-acetyltransferase (SSAT). SSAT activity in cancer cells is higher by several-fold compared
      to normal cells. Amantadine can be used to determine SSAT cellular activity, and may indicate
      the presence of cancer.

      This study will provide additional information in conjunction with data from a previous study
      which include cancer patients and normal health age matched controls to determine whether
      urinary excretion of acetylamantadine is predictive for the presence of cancer, and if so
      whether excretion of this metabolite is associated with any particular site of the tumor.
      Based on the results of the first study additional data in normal healthy volunteers is
      required.

      The data from both studies will be analyzed to account for subject gender, stage of disease
      at time of testing, concurrent diseases, alcohol and tobacco use and occupational
      characteristics. This is an important first step in validating a cancer detection method that
      can be implemented economically for screening of large numbers of people at sites remote from
      limited and expensive diagnostic instrumentation. Thus there is a possibility that this
      design can be prognosis biomarker as well as a positive/negative indicator.
    

Detailed description: 
      A group of 20 female and 20 male normal healthy volunteers ages 18 to 69 will be recruited
      from the community by use of a general advertisement placed initially as posters.

      We will tell the volunteers that we are conducting this study in healthy volunteers to
      determine how amantadine is eliminated from the body. We will explain the pharmacology of
      amantadine and the potential side effects of a single dose before we obtain consent.
      Volunteers will be told of the potential for concurrent alcohol ingestion to result in the
      presence of acetylamantadine in urine. Volunteers will be required to abstain from alcohol
      consumption for at least one day prior to and including the time involved in the amantadine
      ingestion and urine collection. Any previous adverse reaction to amantadine will exclude a
      person from volunteering from this study. Subjects will be informed that side effects from
      this drug ingestion are highly unlikely because only a single dose will be administered. Any
      side effects if they occur will be related to the effect of amantadine on the brain. These
      effects may include insomnia, jitteriness, difficulty in concentrating and mental depression.
      However, these are the side effects associated with chronic ingestion of amantadine and are
      highly unlikely to occur with ingestion of a single dose. Once consent is obtained, the
      volunteers will ingest a therapeutic dose of amantadine (200 mg) in the morning, at least 2
      hours before breakfast, and their complete urine will be collected over a period of 12 hours
      post dose. A previous clinical study in our laboratory with collections of urine for a total
      of 8 hours demonstrated that this collection time was sufficient to collect all metabolically
      produced acetylamantadine in the urine. The urine samples will also be analyzed for their
      content of creatinine as an indication of the completeness of the urine collection. The
      urines will then be labeled with a code and frozen at -20°C until analyzed. The urine will be
      analyzed for acetylamantidine by our established gas chromatography method. The technician
      analyzing the samples will not have access to any participant information other then the code
      on the label. Saliva specimens will also be collected at 2 hour intervals after amantadine
      ingestion. It should be noted that with the morning dose of amantadine collection of multiple
      saliva samples will be simplified and allow for the determination of the optimal time after
      dose for the urine analysis. Furthermore, this design will identify the window of opportunity
      to give the best signal to noise ratio for acetylamantidine production. Blood samples will be
      collected 1 hour prior to dosing and 2 hours post dose.

      We will also collect the following data from each volunteer: their name, age, sex, body
      weight, height, any concurrent medication use, and a recent history of alcohol ingestion.
      These data will be used for correlation analyses to determine any relationship of urinary
      acetylamantidine to the particular cancer diagnosis, sex, and/or the history of alcohol
      consumption. All of these data will be coded by the principal investigator, and individually
      identifying information locked in a secure cabinet. Access to the data by other than the
      principal investigator and/or their attending physician will not be allowed.

      Exclusion criteria are anyone with a history of previous adverse reaction to amantadine as
      well as pregnant or lactating females will be excluded from volunteering for this study.

      Cross validation of the finding will occur by high performance liquid chromatography (HPLC)
      of these urine samples for the presence of polyamines and metabolites, including
      N1-acetylspermidine.
    

Intervention name(s): Amantadine
Intervention type(s): Drug
Intervention description(s): Single dose
Intervention MeSH terms: Amantadine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic