Effects of Mucosave® on Gastrointestinal Discomfort
Condition: Gastrointestinal Discomfort
Study type: Interventional

Summary: 
      Gastrointestinal (GI) discomfort, which often includes gastroesophageal reflux disease (GERD)
      is a common disorder in healthy adults affecting 20% of people particularly women. The
      disorders related to GI discomfort usually have a huge impact on the quality of life. Current
      treatment for GERD are associated with side effects. In this study, researchers designed a
      randomized double-blind placebo-controlled trial to assess the effect of Mucosave® on the
      symptoms and quality of life of healthy adults with gastrointestinal discomfort. One hundred
      healthy subjects with GI discomfort were enrolled in the study and divided in two groups: 60
      and 40 taking for 8 weeks Mucosave® (400 mg/day) or placebo (400 mg/day). To evaluate the
      effects of treatment, the questionnaires Gastrointestinal Quality of Life index (GIQLI) and
      GERD Symptom Assessment Scale (GSAS) were self-administered by participants before the
      beginning of period of supplementation (T0), after four weeks (T4) during the period of
      supplementation and after 8 weeks (T8) at the end of supplementation.
    

Detailed description: 
      Gastrointestinal (GI) discomfort is a common disorder in healthy adults with a prevalence of
      20%, particularly affecting women. Gut health is gaining more interest nowadays for a variety
      of reasons including the well-established link between the body and mind via the brain-gut
      axis. As a result of this connection, GI discomfort is usually accompanied by psychosocial
      factors such as stress and mood disorders. The quality of life can therefore be reduced as
      there is also the occurrence of wide range of disorders, including abdominal pain, sense of
      fullness, nausea, sense of swelling, flatulence, bowel movements, constipation, eructation,
      heartburn and reflux. Gastroesophageal reflux disease (GERD), which is one of the most
      frequent causes of GI discomfort, is a chronic and relapsing disorder that occurs when the
      stomach content reflux into the esophagus. The condition is common in Western countries with
      a prevalence estimated to be about 10-20% while in Asia the occurrence is lower (5%) but is
      expected to increase in a near future. In the United State, 44% of the population report
      having GERD symptoms at least once a month and 20% at least once a week. Due to the
      accelerated pace of life in recent years with an important change in lifestyle, there is an
      increase in GERD incidence. Although GERD is not life threatening, it is characterized by
      important impairment in health related quality of life (HRQL) including a decrease in
      productivity comparable to that of other chronic diseases. In fact, HRQL has been
      demonstrated to be poorer in subjects with frequent upper gastrointestinal tract symptoms
      compared to those with no symptoms as measured by the Psychological General Well-Being Index
      . Beside the typical GERD symptoms like regurgitation and heartburn, impairment of quality of
      life include disturbed sleep, body pain, anxiety and unsatisfactory sex life. The reflux
      episodes can occur on daytime but nocturnal symptoms have an important influence on life
      quality and are associated to the complications of GERD. In addition, GERD symptoms impose a
      substantial cost on healthcare systems. Non pharmacological treatment of GERD include
      avoiding alcohol, coffee, smoking and reducing body weight. On the other hand, current
      pharmacological treatment primarily focuses on the use of proton pump inhibitors (PPIs) for
      the inhibition of gastric secretion. However, there is a persistence of troublesome GERD
      symptoms in 20-30% of patients after a daily treatment with a standard PPI dose. According to
      World Health Organization, about 80% of people in developing countries rely on herbal
      medicine as the first line of treatment. Natural plants present an interesting option for the
      management of gastrointestinal disorders. Opuntia ficus-indica (L.) also known as prickle
      pear is a tropical and subtropical plant usually growing in arid climates especially in the
      Mediterranean and Central America regions thanks to it special adaptative mechanism. In
      Sicily traditional medicine the plant's cladodes are used in the treatment of gastric ulcer.
      This traditional use has been confirmed by scientific studies, suggesting the mucoadhesion
      effect due to the polysaccharides content of cladodes. Wound healing properties are also
      attributed to Opuntia ficus-indica when topically applied on rats. On the other hand, Olea
      europea (Olive) is a mediterranean plant which leaves extract has been shown to prevent
      experimental formation of gastric lesions induced by stress. Other biological activities of
      olive leaves include anti-inflammatory and antioxidant thanks to its abundance in
      polyphenols. Furthermore, a significant correlation has recently been demonstrated between
      gastrointestinal discomfort and microbial dysbiosis. On this basis, the role of intestinal
      microbiota is emerging along with its importance as a new target for treatment.

      A previous clinical study reported the efficacy and the safety for GERD treatment as a
      medical device based on sodium alginate/bicarbonate in combination with Mucosave®, a blend of
      extracts from Opuntia ficus-indica cladodes and Olea europea leaves . In this study,
      researchers performed a double-blinded randomized-controlled trial to assess the efficacy of
      Mucosave® as a sole primary therapy in healthy adults with gastrointestinal discomfort. The
      questionnaires used were the Gastrointestinal Quality of life Index (GIQLI) to evaluate the
      impact of the disorders on the quality of life and the GERD Symptom Assessment Scale (GSAS)
      designed to assess various aspects of GERD. Efficacy in reducing gastrointestinal disorders
      was also measured by the completion of a subjective daily diary.

      Potential participants were subjected to a short medical visit and the inclusion and
      exclusion criteria were assessed and the possibility of inclusion in the study established.
      The study was performed in accordance with the principles of the Declaration of Helsinki.
      Written informed consent was obtained before subjects enrollment.

      Calculation of the sample size The sample size was estimated considering as primary endpoint,
      the increase of the GIQLI score in the study period. Data in the literature show that healthy
      subjects have a GIQLI score variability value of 13.00 and in the present study included
      subjects with a GIQLI score not lower than 90.00. Therefore, considering a value (δ) of
      clinically relevant increase of the score equal to 10, an α value equal to 0.05 and a study
      power of 80%, 55 patients were required to carry out the experimentation. In order to
      guarantee the power, a possible abandonment rate of 8% was also considered, consequently a
      total number of 60 subjects supplied with Mucosave® is necessary to be guaranteed the
      endpoint of the study.

      Screening and Randomisation Before enrollment subjects were asked to respond to the GIQLI and
      GSAS questionnaires with the aim to establish basal level score of participants.

      Intervention Allocation of participants into the group supplied with Mucosave® or placebo was
      performed through computerized randomization. A total of 100 participants were enrolled. They
      were divided in two groups: 60 healthy volunteers taking 400 mg/day of Mucosave® capsules and
      40 healthy volunteers taking capsules of placebo for a period of 8 weeks, once a day after
      dinner before going to bed. Mucosave® (Bionap srl, Italy) is a blend of two enriched extracts
      from Opuntia ficus-indica cladodes (32-35% w/w) and Olea europea (olive) leaves (23-25% w/w)
      with a total polyphenol amount of 3.7-4.3% as luteolin 7-O-glucoside with maltodextrin as
      support.

      Assessment Compliance with test beverage consumption was self- recorded daily by participants
      in a diary. Subjects were reminded of the behavioural modalities related to the study: dosage
      of treatment and abstinence from taking anti-reflux drugs such as PPIs, histamine-2 blockers,
      agents facilitating motility or other antacids.

      The primary endpoint of the study was defined as relief of gastrointestinal disorders
      evaluated by GIQLI and GSAS at the beginning (T0), after four weeks (T4) and eight weeks (T8)
      of supplementation period between the group of subjects supplied with Mucosave® and group
      supplied with placebo.

      The Gastrointestinal Quality of Life Index (GIQLI) questionnaire contains 36 questions, each
      with 5 answers in the "Likert scale" style (technique for measuring the attitude): the range
      goes from 0 (always answer with letter "a") to 144 (always answer with letter "e"), according
      to the meaning "higher score, better quality of life". Patients with more severe
      gastro-intestinal disorders generally reach an average score corresponding to 45 points,
      compared to the median score 126 of healthy controls. Investigators analyzed answers and
      evaluated the scores only for the following disorders: abdominal pain, sense of fullness,
      sense of swelling, flatulence, eructation, bowel sounds, bowel movements, reflux,
      constipation, nausea and heartburn. Increase in scores corresponds to reduction of disorders.

      GSAS is the most complete evaluation scale of gastrointestinal symptoms. The GSAS is a
      15-item tool designed to evaluate various aspects including stress about gastrointestinal
      symptoms before and after treatments. It is a simple and easy to understand tool that can be
      administered in a relatively short time. GSAS is valid, stable and sensitive to changes in
      symptom over time.

      At the same time each participant received a daily diary in which they found a few simple
      multiple choice questions, which helped the investigators to establish the individual degree
      of satisfaction of treatment. Each participant was asked to answer for the first 15 days of
      treatment with Mucosave® or placebo to the following questions: How are you today?, How are
      you compared to yesterday?, Have you had heartburn today?, have you had abdominal swelling
      today?, Have you had belching today?, Which symptoms were improved today?.

      The symptom diaries and questionnaires were coded and anonymized. Codes were broken only
      after the raw data had been entered into the database.
    

Intervention name(s): Mucosave® capsules; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 400 mg/day of Mucosave® capsules for a period of 8 weeks, once a day.; 400 mg/day of placebo capsules for a period of 8 weeks, once a day.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, controlled, double blind study
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Gastrointestinal symptoms; Nausea; Heartburn; Reflux