Zinc Supplementation to Reduce Diarrhea Rates in Adults in Western Kenya.
Condition: Diarrhea; Malaria
MeSH terms: Malaria; Diarrhea
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Zinc deficiency is prevalent in children in developing countries. Zinc-supplementation is
      proven to reduce the duration and severity of childhood diarrhea in randomized controlled
      trials. However, despite this evidence, its efficacy to reduce diarrhea morbidity in adults
      remains unknown. The main objective of this study is to determine the efficacy of
      Zn-supplementation on diarrhea incidences in a vulnerable adult population. The study will be
      carried out in Kombewa division, Kisumu District and will involve 500 adults aged 18-55
      years. They will be randomly assigned to receive Zn supplement (or placebo) on a daily basis
      over a 3 month period. Morbidity information will be collected daily for 4 months, while
      anthropometric measures and laboratory data will be obtained at study onset, end of
      supplementation and study conclusion. In addition, HIV and malaria tests will be carried out
      during the study as they are important confounders. The significant differences in diarrhea
      incidence between the Zn-group and the placebo-group will be determined using SPSS. The
      results are expected to provide the scientific basis and common pathway for development of an
      anti-diarrheal supplement for vulnerable populations such as environmental refugees, deprived
      and displaced persons, and troops prior to deployment.
    

Detailed description: 
      Diarrhea has been a major cause of morbidity, hospitalization, and loss of duty days for
      military personnel for centuries. In fact, diarrheal illness is the most common medical
      problem for U.S. troops during operational deployment. Soldiers are especially prone to
      diarrhea because of travel, consumption of locally procured foods (including raw vegetables
      and poorly-cooked meat products) and the use of nonpotable water, or ice. High rates of
      occurrence continue to be reported in soldiers deployed to recent conflicts. Furthermore,
      high morbidity rates from enteric disease have been reported by other military forces in
      areas of current combat operations: up to 53%-69% of Soviet troops had major gastrointestinal
      infections during the Afghanistan war, and up to 69% of British troops and 36% of Australian
      troops reported diarrhea in Iraq during Operation Safe Haven in 1991.

      The region of sub-Saharan Africa, where the proposed study would be conducted, is uniquely
      positioned for anti-diarrheal research that can offer answers to problems of the civilian
      population, displaced persons and deployed soldiers or workers in remote areas. Diarrheal
      disease is the 4th leading cause of out-patient morbidity in Kenya, accounting for almost 5%
      of all new outpatient cases, with a higher prevalence in Nyanza Province - 5.4% to 7.1% of
      total new cases. Kisumu lies in the Nyanza Province in western Kenya, bordering Lake Victoria
      and populated by the Luo ethnic group. Nyanza is one of Kenya's most impoverished provinces
      with one of the nation's lowest immunization rates, highest infant mortality and highest
      prevalence of HIV (35% among adults 15-49 years old in 2000, as compared to 14% nationally).
      Malnutrition is common; endemic diseases include malaria, leishmaniasis, tuberculosis and
      schistosomiasis.

      Scientists from the Centers for Disease Control and Prevention (CDC) have reported on the
      species of bacterial pathogens isolated from diarrhea patients in the Kisumu area: the
      bacterial isolates were similar to those reported in U.S. soldiers (44% Shigella; 30%
      Campylobacter; 14% Salmonella). However, most of the isolates (51%) were not susceptible to
      their antimicrobial treatment. The study by Brooks et al. (2003), reported that more than 90%
      of the isolates (excluding Campylobacter) were resistant to trimethoprim-sulfamethoxazole and
      tetracycline, and more than 80% were resistant to ampicillin.

      If this alarming trend persists, and drug-resistant bacteria are identified in civilian
      populations, gains in disease control strategies already deployed will not be achieved, and
      in case of deployed members of the military or workforce, mission-impact may be severely
      compromised. Thus, we propose that the Kombewa Clinical Research Center (KCRC), located
      outside of Kisumu, would allow for testing of a novel anti-diarrheal treatment, specifically
      dietary zinc (Zn), in antibiotic-resistant bacteria with potential benefits to not only the
      deployed U.S. military and western Kenyan populations, but also other populations in Africa.
      Populations living in the Kombewa area will serve as potential study volunteers because of
      the high prevalence of antibiotic-resistant diarrhea in adults in this region.

      This study will build upon the proven concept that Zn-supplementation, as an adjunct to oral
      rehydration, is highly protective against diarrhea in children. The results are expected to
      provide the scientific basis and common pathway for development of a commercially viable,
      multivalent, food-based, anti-diarrheal supplement for vulnerable populations such as troops
      prior to deployment, deprived and displaced persons. Based on a successful outcome, we would
      expect to attract commercial support for a final micronutrient formulation suitable for field
      use and expanded efficacy evaluation in pivotal studies for support of licensure. An
      anti-diarrheal product for adults will fill an important military, refugee population need
      and have dual use in the civilian sector.

      The benefits of maintaining adequate zinc status in populations in tropical areas and more so
      displaced populations such refugees and deployed soldiers are probably not limited to the
      disease states discussed here. Roles for Zn have been described for other important issues
      facing the soldier and populations in the tropics especially children, including cutaneous
      leishmaniasis, malaria, pneumonia, wound healing, cognitive function and behavior, and night
      vision. Because of these important roles for Zn in maintaining health and fighting disease,
      maintaining adequate Zn levels and supplementing with Zn in some cases, should be considered
      when formulating diets for resource deprived populations, displaced people and the modern
      deployed soldiers.

      The primary objective of the study is to determine the incidence of diarrhea in zinc vs.
      placebo-supplemented adults; secondary objectives include: determining the time to diarrhea
      onset in both groups; determining the duration of each diarrhea episode in both groups; and
      determining the number of loose stools per day per episode of diarrhea in both groups.
      Tertiary objectives include determining the nutritional status of the study population by use
      of anthropometric measurements and micronutrient assays; determining the incidence of malaria
      in zinc vs. placebo-supplemented adults; and determining if HIV infection is a confounding
      factor in the outcome of diarrhea incidences following zinc supplementation in adults.

      Hypotheses

        1. There is no statistically significant difference in the incidence of diarrhea in adults
           when given Zn supplementation as compared to placebo over a three month period. We will
           determine the incidence of diarrhea in both the Zn and placebo arms of the study. This
           will be accomplished from self-reported incidence of volunteers collected by health
           workers at the field stations or at the subject's home.

        2. The time to diarrhea onset will not be significantly different in the Zn supplemented
           study arm as compared to the placebo study arm. We will determine the number of days
           from the study start (this will be after a two week period of volunteers receiving
           either Zn supplements or placebo) until onset of diarrhea in both the Zn and placebo
           arms of the study. This will be accomplished from self-reported data of volunteers
           collected by health workers at the field stations or at the subject's home.

        3. The duration of each diarrhea episode will not be significantly different in the
           Zn-supplemented study arm as compared to the placebo study arm. We will determine the
           number of days of each diarrhea episode in both the Zn and placebo arms of the study.
           This will be accomplished from self-reported data of volunteers collected by health
           workers at the field stations or at the subject's home.

        4. The number of loose stools per day per episode of diarrhea will not be significantly
           different in the Zn-supplemented study arm as compared to the placebo study arm. We will
           determine the number of number of loose stools per day per episode of diarrhea in both
           the Zn and placebo arms of the study. This will be accomplished from self-reported data
           of volunteers collected by health workers at the field stations or at the subject's
           home.

        5. The incidence of malaria will not be significantly different in Zn vs.
           placebo-supplemented adults. We will determine the incidence of malaria in both the Zn
           and placebo arms of the study. This will be accomplished using the results from the
           malaria blood smears collected during the study.
    

Intervention name(s): Zinc sulphate; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Volunteers will be randomly assigned to either receive zinc sulphate supplements (20 mg/capsule) or a placebo containing no zinc. Maltodextrin serves as the carrier. The manufacturer is Tishcon Corporation, Westbury, NY.; Volunteers will be randomly assigned to either receive zinc sulphate supplements (20 mg/capsule) or a placebo containing no zinc. Maltodextrin serves as the carrier. The manufacturer is Tishcon Corporation, Westbury, NY.
Intervention MeSH terms: Zinc Sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: diarrhea morbidity; malaria incidence; zinc supplementation