Echinacea and Acute Respiratory Illness
Condition: Acute Respiratory Infections
MeSH terms: Respiratory Tract Infections
Study type: Interventional

Summary: 
      The primary objective of this study is to evaluate the effectiveness of ingesting an
      alkylamide-rich echinacea root product (Quick Defense, Gaia Herbs) for 2 days immediately
      following each onset of acute respiratory illness (ARI) symptomatology during a 12-week
      period in the winter and early spring in women.

      Hypothesis: Subjects randomized to Quick Defense compared to placebo over a 12-week period
      will experience reduced ARI symptomatology, both acutely during each ARI episode and
      collectively over the entire 12-week study period.
    

Detailed description: 
      The common cold is an acute respiratory illness (ARI) and the most frequent illness people
      experience, with economic costs estimated at $40 billion per year (Ann Intern Med
      2010;153:769-777). Hundreds of different types of viruses cause the common cold, and
      etiologic agents include rhinovirus, coronavirus, influenza, parainfluenza, respiratory
      syncytial virus, adenovirus, enterovirus, and metapneumovirus.

      The purple coneflower (E. angustifolia and E. purpurea) is one of the most popular herbal
      supplements in North America and Europe. Echinacea preparations are marketed to provide
      protection and treatment for the common cold. Reviews and meta-analyses provide modest
      support for the use of Echinacea in the prevention and treatment of the common cold (Can Fam
      Physician 2011;57:31-6; Cochrane Database Syst Rev 2006 Jan 25;(1):CD000530; Lancet Infect
      Dis 2007;7:473-80; Clin Ther. 2006 Feb;28(2):174-83). One meta-analysis concluded that
      echinacea decreased the odds of developing the common cold by 58% and the duration of a cold
      by 1.4 days (Lancet Infect Dis 2007;7:473-80).

      Echinacea products vary in their composition, due to the use of different species, plant
      parts, extraction methods, and addition of other components (Planta Med 2008;74:633-7). Some
      preparations are based on the stabilized fresh juice of aerial parts of E. purpurea, and are
      rich in hydrophilic derivatives such as polysaccharides and glycoproteins. Other echinacea
      products come from an extract of root material and contain more lipophilic compounds
      including N-alkylamides (Ann Intern Med 2010;153:769-777).

      Studies indicate that echinacea preparations containing N-alkylamides are bioavailable in
      humans and can suppress stress-related cellular immune responses (Life Sci
      2009;85(3-4):97-106). Echinacea preparations containing N-alkylamides have been linked to
      multiple immune-modulatory activities including enhanced macrophage phagocytic activity and
      suppression of the proinflammatory responses of epithelial cells to viruses and bacteria (J
      Biomed Biotechnol. 2012;2012:769896). Echinacea preparations appear to have low potential to
      generate cytochrome P450 (CYP 450) drug-herb interactions, and there are no verifiable
      reports of drug-herb interactions. The estimated risk of taking echinacea products is 1 in
      100,000, and thus do not appear to pose a risk to consumers (Mol Nutr Food Res.
      2008;52(7):789-98).

      Barrett et al. (Ann Intern Med 2010;153:769-777) enrolled subjects within 36 hours of illness
      onset, and administered echinacea tablets (or placebo) containing 675 mg E. purpurea root
      standardized to 2.1 mg alkamides and 600 mg E. angustifolia root standardized to 2.1 mg
      alkamides. Subjects consumed two tablets at enrollment, followed by two-tablet doses three
      more times within 24 hours of enrollment. Dosing then went to one tablet four times daily for
      the next four days. Thus, each participant ingested the equivalent of 10.2 g of dried
      echinacea root during the first 24 hours and the equivalent of 5.1g during each of the next
      four days. Results were in the direction of benefit, amounting to an average half day
      reduction in the duration of a week-long cold, or an approximate 10% reduction in overall
      severity.

      The proposed study will build upon the study by Barrett et al., (2010) by initiating 2-day
      use of an alkylamide-rich echinacea root product (Quick Defense, Gaia Herbs) within the first
      few hours of each ARI onset throughout a 12-week period in the winter/early spring.

        1. DESIGN GUIDELINES:

             1. Following recruitment, subjects will come to the ASU-NCRC Human Performance Lab
                (visit 1 or pre-study visit) for orientation and to provide voluntary consent to
                join the study. All subject inclusion and exclusion criteria must be maintained
                during the study.

             2. Subjects will fill in a medical health questionnaire to verify medical history and
                lifestyle habits (completed and handed in at visit 1).

             3. Subjects will have two additional laboratory visits (6-weeks and 12-weeks) at the
                ASU-NCRC Human Performance Laboratory.

                At each of the three lab visits, body weight and percent body fat (Tanita BIA
                scale) will be measured. Height will be measured at the pre-study visit. At each
                lab visit, subjects will also record responses to 6-week retrospective symptom
                logs. At the pre-study and 6-week study visits, subjects will be given 6-week daily
                log books, the Wisconsin Upper Respiratory Symptom Survey (WURSS-24), to assess
                symptoms related to the common cold. Subjects will turn this in during the 6-week
                and 12-week visits. Subjects will fill in a 6-week retrospective WURSS-24 during
                visit 1. Subjects will be interviewed by the lab staff at weeks 6 and 12 to
                determine whether there have been any changes in their medical history or
                medication use.

             4. Subjects (N=40-46) will be randomized to Quick Defense or placebo groups for 12
                weeks (thus two independent groups with 20-23 subjects). Supplements will be
                administered in a double-blinded manner, with the code held by Gaia Herbs until the
                end of the study.

        2. SUPPLEMENT:

      Echinacea (Quick Defense) and identical placebo capsules will be manufactured by Gaia Herbs
      (Brevard, NC). Gaia Herbs will conduct an analysis of their product to verify supplement
      content. Two echinacea capsules will contain the equivalent of 250 mg E. purpurea root and 83
      mg E.angustifolia root standardized to 10 mg alkylamides, and 210 mg of a proprietary
      synergistic extract blend containing andrographis paniculata leaf, black elderberry berries,
      sambucus nigra, ginger root, and zingiber officinale (see label above). Capsule excipients
      will include vegetable glycerin and olive oil, with the capsule containing vegetable
      cellulose. Placebo and echinacea capsules will be colored green and contain the same
      proportions of inert ingredients.

      DOSING REGIMEN:

      During the 12-week study, subjects will take 2 capsules 5 times daily (approximately every 3
      hours) for 2 days each time they feel symptoms of an acute respiratory illness (ARI) are
      starting. Thus each subject will ingest the equivalent of 3.4 grams of dried echinacea root
      during the first two days of ARI onset. No additional echinacea (or placebo) capsules will be
      taken after the first two days of illness onset until the next ARI episode is experienced.

      c. COMMON COLD SYMPTOMS: The Wisconsin Upper Respiratory Symptom Survey (WURSS-24) will be
      used to assess common cold illness severity and symptoms (see attached questionnaire). Scores
      from the WURSS-24 include: 1) Global severity score; 2) Symptom score; 3) Function ability
      score (Barrett et al., 2009). The WURSS-24 (short version to be used in this study) includes
      10 items assessing symptoms (running nose, plugged nose, sneezing, sore throat, scratchy
      throat, cough, hoarseness, head congestion, chest congestion, feeling tired), 9 items
      assessing functional impairments (think clearly, sleep well, breathe easily, walk-climb
      stairs-exercise, accomplish daily activities, work outside the home, work inside the home,
      interact with others, live your personal life), and 1 item assessing global severity and
      global change. Subjects will fill in the one-page WURSS-24 at the end of each day during the
      12-week monitoring period. This 12-week period will cover the winter and early spring period
      of 2014. From the responses recorded during the 84-day study, an ARI severity score will be
      calculated by summing the daily ARI global severity score (0=not sick, 1=very mild ARI to
      7=severe). The ARI symptom score for the 84-day period will be calculated by summing all 10
      symptom scores for each day's entry (0=do not have this symptom, 1=very mild to 7=severe). In
      similar fashion, the ARI function ability score for the 84-day period will be calculated by
      summing all 9 function scores for each day's entry (0=do not have this symptom, 1=very mild
      to 7=severe). Separate scores will be calculated comparing groups for each illness episode
      recorded by the subjects.
    

Intervention name(s): Quick Defense; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Echinacea product from Gaia Herbs.; Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Common cold