Aquamin and Prevention of Colon Cancer
Condition: Colonic Cancer
MeSH terms: Colonic Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      In the proposed study, investigators will conduct a 90-day dietary intervention study in
      human subjects. Thirty individuals at risk for adenomatous colon polyp formation will be
      randomized to receive a calcium and multi-mineral-rich natural product (Aquamin) or a
      comparable level of calcium alone. There will also be a placebo group. Prior to ingesting the
      study agents and following the course of treatment, colonic biopsies will be obtained by
      sigmoidoscopy and quantitatively examined for markers of growth and differentiation. In this
      study, metabolomic and microbial profiles will also be generated from fecal and colon mucosal
      samples taken at baseline and study endpoint.
    

Detailed description: 
      The purpose of this study is to see what effects a calcium-rich, multi-mineral-rich natural
      product, Aquamin®, derived from marine algae, has compared to calcium alone or a sugar pill
      (placebo). Investigators are looking at whether these supplements do anything to the cell
      lining of the colon. Specifically, to see if Aquamin®, calcium, or placebo (sugar pill)
      change markers of cell growth and differentiation (or "biomarkers") in the cells of the
      colon. The natural product, Aquamin®, contains calcium but, in addition, has a significant
      amount of magnesium and measurable levels of approximately 70 different trace elements
      (essentially, everything the algae can accumulate from seawater). Aquamin is a product that
      is marketed for the fortification of food, beverage, and supplement products. In this study,
      it is being used for research and therefore, its use is investigational. Calcium supplements
      have been shown to reduce colonic polyps (precursor lesions to colon cancer). This study will
      NOT look at polyp formation in the colon, but only at biomarkers of colon cell growth and
      function. If investigators find that the multi-mineral natural product is substantially more
      effective than calcium alone in changing these biomarkers, it is possible that a larger study
      could be conducted that is intended to study colon polyp prevention. In order to test these
      ideas investigators need to compare the supplement Aquamin®, to something already tested
      (calcium) and a placebo (sugar pill) to see if any changes are related to the supplements or
      just naturally happen.

      There is increasing recognition that dietary or environmental predispositions to colorectal
      cancer may be mediated at least in part by alterations of gut microbial composition and
      metabolomic profiles. Human gut microbiota are now recognized to play an important role in
      host health and changes in the composition of gut microbial communities have been linked with
      metabolic alterations that affect colorectal cancer risk. Investigators have previously
      established that dietary supplementation can correlate with metabolic or microbial
      alterations in their most recent long-term study in mice on high-fat western diet (HFWD) and
      calcium. Investigators had also demonstrated that Aquamin-supplemented mice had significantly
      decreased liver and colon tumors. Based on these studies, investigators anticipate that
      Aquamin will improve the gut microbial composition and alter the metabolomic profile in these
      subjects.

      If participant agree to participate in this research study, he/she will be asked to sign this
      informed consent document before any tests are performed or data collected. This research
      study consists of three time periods (phases): a pre-treatment period; a study treatment
      period; and an end-of-study treatment period. The study requires three visits to the
      University of Michigan's Clinical Research Unit (MCRU). These are referred to as the
      Screening Visit, Baseline Visit and Final Visit.

      After participants are determined to meet eligibility requirements, they will be randomized
      as to which product they will receive. Randomization is like a flip of a coin. A participant
      will have an equal chance (33.3%) of being given one of three assignments: a multi-mineral
      natural product (Aquamin®); a calcium-only supplement; or a placebo ("sugar pill"). Each
      participant will be required to take four capsules per day (two taken in the morning and two
      in the evening) for 90 days. Neither they nor the study team investigators will know which
      product they are receiving. That information will be kept in the hands of the pharmacist who
      dispenses the agent that participant will take.

        -  Each participant will be given a physical examination, which will include measurements
           of his/her height, weight, and vital signs (temperature, blood pressure, heart rate,
           breathing rate).

        -  The study nurse or physician's assistant will review participant's past medical history.

        -  Participants will be asked about any other medical conditions that they may have and all
           medication(s) they are currently taking. It is important that participants tell the
           study personnel about any medications they are taking including over-the-counter
           medications, calcium supplements with or without vitamin D, other vitamins, herbal
           medications and alternative medicines. Participants may need to stop some of their
           medicines in order to participate in this study. Participants are instructed to inform
           study personnel at any time during the study participation if they begin to take any
           medication(s).

        -  Study participants will be asked about their intake of foods and supplements containing
           calcium and vitamin D.

        -  Participants will be asked to provide information regarding their usual food that they
           eat (over a year), past year diet history questionnaire (DHQ II)

        -  Participants will be asked to take a pregnancy test within 14 days before the start of
           the study if she is a woman able to become pregnant.

        -  Participants will be asked to not take calcium, vitamin D, fiber, ginger, or fish oil
           supplements (including multivitamins that have low amounts) for 14 days before the study
           begins and for 90 days after the study begins.

      Study Treatment Period (Baseline Visit through day 90) The second visit will take place
      within 60 days of the screening visit at the MCRU. This visit will take about 1.5 hours.

      During this Baseline Visit, the following will be performed:

      • Each participant will have a flexible sigmoidoscopy with colon biopsies (where twelve
      tissue pieces will be removed). At this time a stool sample will also be collected using the
      sigmoidoscope. The flexible sigmoidoscopy will be done without bowel preparations such as
      those used before a colonoscopy. A gastroenterologist who routinely does this procedure will
      do the sigmoidoscopy and remove the tissue / stool samples.

      Flexible sigmoidoscopy is a test that allows the investigators to look at the inside of the
      colon (large intestine) from the rectum up to 15 centimeters (about 7 inches) into the colon.
      For the flexible sigmoidoscopy, subject will lie on its left side on the examining table. The
      investigator will insert a short, flexible, lighted tube into the rectum and slowly guide it
      into the colon. The tube is called a sigmoidoscope (sig-MOY-duh-skope). The scope transmits
      an image of the inside of the rectum and colon so the investigators can carefully examine the
      lining of participant's colon. The scope also blows air into the colon, which inflates it and
      helps the investigators to see better. During the flexible sigmoidoscopy, the investigator
      will remove several small pieces of the lining of the colon (these are called colon biopsies)
      using forceps instrument inserted into the scope. Each of the two sigmoidoscopy procedures
      (one at the beginning of the study and the other after the participant have completed taking
      the agent) requires twelve biopsies (5 mg each; about the size of a grain of wheat).

        -  Each participant will have 10 ml (or 2 teaspoons) of blood drawn from a vein.

        -  Each participant will be requested to give a fresh urine sample which will be collected
           at the beginning of this visit, before sigmoidoscopy.

        -  At the end of this visit (Baseline Visit), all participants will receive the assigned
           study agent and instructions for taking the study agent.

      Between the beginning of the study treatment period and the end of the study (days 1 through
      90):

      Participants will take capsules containing the assigned study agent (the multi-mineral
      natural product or calcium or placebo) for 90 days. This will entail taking a total of four
      capsules per day.

      The capsules should be taken as follows:

      Two in the morning and two in the evening. It is suggested that they be taken at meals, but
      this is not required. Subjects can ingest the capsules with as much liquid that they choose.

      Participants must avoid starting any new medications or supplements, such as over the counter
      calcium supplements (with or without vitamin D), as well as systemic (by mouth)
      corticosteroids such as Prednisone and Cortisol. Also, participants should not begin a course
      of antibiotic with any cephalosporin antibiotic including rocephin, keflex or omnicef. If
      participants are prescribed a cephalosporin antibiotic during the course of study, discuss
      this with their physician and the study team. Also, once a month each participant will
      receive a phone call or email from the researchers to determine whether they are experiencing
      any problems related to the study or any side-effects and to ask how many capsules each
      participant has taken. If a participant is a woman who is able to get pregnant, she must use
      a reliable method of birth control throughout the study. If a participant thinks she might be
      pregnant, she should contact the study team immediately. The study team will arrange for a
      pregnancy test.

      End of Study Treatment Period (Final Visit) (Day 90)

      Within a week after Day-90, each participant will have his/her last visit at the MCRU. This
      Final Visit will take about 1 hour. During the End of Study Treatment Final Visit, the
      following will happen:

        -  Participants will have a second flexible sigmoidoscopy (where twelve colon biopsies will
           be taken as well as stool samples).

        -  Participants will answer a questionnaire about whether they believed they received the
           Aquamin®, calcium or the placebo capsules, any untoward effects of the agents and the
           overall study experience.

        -  Participants will return any unused capsules and answer questions about any study drug
           they did not take.

        -  Each participant will have 10 ml (or 2 teaspoons) of blood drawn from a vein.

        -  Each participant will be requested to give a fresh urine sample which will be collected
           at the beginning of this visit, before sigmoidoscopy.

        -  Participants will tell the researchers if they had any negative reactions, side-effects,
           or problems over the last month of the study.
    

Intervention name(s): Aquamin®; Calcium Carbonate; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 90 days of Aquamin; 90 days of Calcium Carbonate; 90 days of placebo
Other intervention name(s): Maltodextrin
Intervention MeSH terms: Calcium Carbonate; Calcium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Colon polyp; Colorectal cancer; Chemoprevention; Natural product