Hydrogen Water Treatment for Chronic Fatigue Syndrome
Condition: Chronic Fatigue Syndrome
MeSH terms: Fatigue Syndrome, Chronic; Syndrome; Fatigue
Study type: Interventional

Summary: 
      The proposed placebo-controlled pilot study will examine hydrogen water as a treatment for
      myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). 25 subjects who meet strict
      criteria for ME/CFS will be recruited. The 30 day trial will involve subjects ingesting 1-5 8
      oz. glasses of hydrogen-dissolved water per day. The placebo condition will involve the same
      daily ingestion schedule but with an inert placebo pill instead of the active hydrogen
      treatment pill. The proposed study is intended to establish feasibility of the clinical
      protocol and examine potential treatment effects of hydrogen water which may include symptom
      reduction and possibly improved functioning. If feasibility and apparent treatment effects
      are confirmed, a large clinical trial will be proposed for submission to NIH. In addition to
      potential therapeutic properties, H2 water is portable, easily administered and safe to
      ingest.

      Self-report assessments for ME/CFS symptoms, fatigue, autonomic symptoms, physical function,
      anxiety, and depression will be done in the week before and the week after the 30 day trial.
      In addition, 7-day home-based objective assessments of heart rate variability (a measure of
      parasympathetic function) and accelerometry (a physical activity assessment) will be
      scheduled before and after the intervention period.
    

Detailed description: 
      SPECIFIC AIMS

      The aim of this pilot randomized control trial (RCT) is to explore the possible beneficial
      effect of a novel therapy, molecular hydrogen (H2) for the symptoms and related functional
      limitations in patients with chronic fatigue syndrome.

      BACKGROUND AND SIGNIFICANCE Oxidative stress and impaired energy metabolism have been
      implicated in the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome
      (ME/CFS), a debilitating illness without clearly identified etiology or effective medical
      treatments. As such, treatments that reduce oxidative stress and yield improvements in energy
      production may show potential to ameliorate the symptoms and functional limitations of this
      illness. Numerous publications on the biological and medical benefits of H2 have shown that
      H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also
      indirectly by regulating various gene expressions. In addition to its potential therapeutic
      properties for ME/CFS, H2 water is portable, easily administered and safe to ingest.

      PRELIMINARY STUDIES

      The proposed study is a pilot study in ME/CFS for which there are no directly applicable
      preliminary studies utilizing the proposed H2 therapy.

      RESEARCH DESIGN AND METHODS

      Eligible subjects will be recruited by advertising. Assessments will be conducted by
      telephone, via home-based monitoring, and online diaries. The PI has 16 years' experience
      recruiting ME/CFS patients for his NIH funded studies. Given the absence of effective
      interventions for this illness and the absence of in-person visits in the proposed study, the
      possibility of being helped by the benign treatment of H2 is likely to attract many patients
      with ME/CFS.

      Study Sample

      Subjects who meet the inclusion/exclusion criteria below and provide consent will be
      recruited and randomized sequentially 1:1 to receive either H2 or placebo. The investigators
      will seek to enroll a total of 25 patients meeting enrollment criteria and randomized to H2
      vs placebo arms. The investigators project a study duration of 8-10 months.

      Screening

      Inclusion criteria: These are: patients aged 18-65 of both sexes considered physically
      capable and willing to perform the study tasks, including wearing a heart monitor and an
      actigraph (at baseline and post-treatment weeks). Subjects must also meet our validated
      phone-screen eligibility for ME/ CFS criteria. A physician note confirming a CFS diagnosis
      will be requested.

      Medical exclusions, determined by validated phone screen interview, will consist of cases of
      fatigue clearly attributable to self-report medical conditions such as untreated
      hypothyroidism, unstable diabetes mellitus, organ failure, chronic infections, and chronic
      inflammatory diseases, or AIDS. Exclusionary psychiatric disorders include any psychosis, or
      alcohol/ substance abuse within two years prior to illness onset and any time afterward, and
      current or past depression with melancholic or psychotic features within 5 years prior to
      onset of ME/CFS or anytime afterward. Pregnancy, as determined by reliable home test kit sent
      to subjects, is also an exclusion. Two other exclusionary criteria will be used: a) patients
      on heart medication or patients not dose-stabilized for at least 3 months on antidepressant
      drugs; b) patients at significant risk of suicide or in need of urgent psychiatric treatment.
      As much as possible, appropriate medical and psychiatric referrals to facilities local to
      subjects will be provided.

      Procedures/Outcome measures

      This will be a double blinded, placebo-controlled trial. Subjects will be sequentially
      randomized in a 1:1 ratio to receive H2, or corresponding placebo, additional to all
      standard-of-care treatments. All study-related participant activities, including
      questionnaires, activity and heart monitoring, and online diaries will be completed by
      participants in their homes. No face-to-face visits to Stony Brook are involved. H2 water is
      Generally Recognized As Safe (GRAS) and is increasingly available on the general consumer
      market. Self-report questionnaire assessments for ME/CFS symptoms, fatigue, autonomic
      symptoms, physical function, anxiety, and depression will be done in the week before and the
      week after the 30 day trial. In addition, an online web diary to record ME/CFS symptoms and
      home-based objective assessments of heart rate variability (a measure of parasympathetic
      function) and accelerometry (a physical activity assessment) will be scheduled before,
      during, and/or after the intervention period.

      STATISTICS The study will define improvement by a 50% reduction in ME/CFS symptoms. Repeated
      measures analysis of variance (ANOVA) will compare pre- and post-treatment measurements of
      effectiveness and general health markers.
    

Intervention name(s): Hydrogen water
Intervention type(s): Dietary Supplement
Intervention description(s): This is an over the counter pill supplement that is dissolved in water.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This clinical study involves two groups, one group receiving only the active treatment, hydrogen pills mixed with water, and the other group receiving only a placebo pill mixed with water.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: hydrogen; treatment