BERRY- a Study of Sambucol ® in the Treatment, and Reduction of Symptoms in Participants With Coronavirus 19
Condition: COVID-19
MeSH terms: Coronavirus Infections
Study type: Interventional

Summary: 
      Severe acute respiratory syndrome (SARS) coronavirus 2 (CoV 2) (COVID19) is a readily
      transmissible virus that has a wide ranging incubation period of 2-14 days. The symptoms
      include fever, cough and loss of taste and smell. Symptoms range from mild to severe.
      Pre-existing potential drug therapies are under investigation, but so far few have
      demonstrated any benefit and only in patients with severe symptoms. There is a scarcity of
      other pre-existing drug treatments that change the outcomes/symptoms in non-hospitalised
      patients with COVID-19.

      Prophylaxis and prevention is currently dependent on social distancing and isolating with
      vaccines remaining in development, potentially not for mass use in the near future.

      Sambucus extract has well documented anti-viral properties both in vitro and in clinical
      trials of influenza, it has a low side effect profile so may be effective in reducing
      duration of symptoms and progression to more severe disease in patients with mild/ moderate
      COVID19. Black Elderberry Original Liquid (Sambucus nigra) (Sambucol®) is sold as a food
      supplement in heath food shops and supermarkets, does not require a prescription and has no
      known side effects, meaning it would be a well-tolerated treatment in early disease in
      comparison with other potential medications.

      The study will be conducted at East Kent Hospitals. Potential participants with mild or
      moderate confirmed COVID19 infection will be identified from the drive-through hospital test
      centre and accident and emergency.

      Following an eligibility check and consenting they would be randomised to placebo or
      Sambucol® Black Elderberry (Sambucus nigra) 15ml four times daily for 14 days which they will
      take at home. Telephone consultations with the research team and patient daily diaries will
      used to document symptoms on days 1,3,7,10,14 and a follow up on day 28. Time to clinical
      improvement will be compared between the 2 groups.
    

Detailed description: 
      The outbreak of the new coronavirus SARS-CoV-2 (COVID-19) in China has rapidly progressed to
      pandemic status of global importance. The current lack of a proven anti-viral that is
      effective has meant the current management of severe respiratory coronaviruses remains
      supportive. The success achieved in treating bacterial infections is not paralleled in
      antivirals. The relative paucity lies in a lack of drugs that stop replication within a
      living cell, and that the peak rate of growth may occur prior to symptoms.

      A randomised controlled trial of lopinavir/ritonavir (an antiviral treatment commonly used to
      treat HIV) compared to standard of care in patients with severe COVID-19 demonstrated no
      clinical benefit and in 13.8% treatment had to be stopped early due to adverse events .
      Prophylactic use of hydroxychloroquine continues worldwide both within and outside of
      clinical trials but concern remains with prescribing an unproven drug with well-known adverse
      neurological and cardiac effects .'RECOVERY' is a large United Kingdom (UK) randomised
      controlled trial established to test a range of potential treatments for COVID-19 in
      hospitalised patients, including lopinavir/ritonavir and hydroxychloroquine. Over 12,000
      patients have been enrolled from 176 National Health Service (NHS) hospitals. It showed no
      benefit of hydroxychloroquine nor lopinavir/ritonavir in this population, and by contrast,
      that low-dose dexamethasone reduces the risk of death by about one-third among patients
      receiving ventilation and by one-fifth in those requiring oxygen alone. However, no benefit
      was demonstrated amongst those not requiring respiratory support. Pharmacognosy is the study
      of medicines derived from natural sources. Plant extracts have been widely used to treat a
      number of medical conditions, with some of the best-known examples including, quinine
      isolated from Cinchona pubescens (cinchona tree) used to treat malaria, Papaver somniferum to
      make morphine and Digitalis purpurea for treating atrial fibrillation. A number of plant
      constituents have demonstrated anti-viral activity. Hippocrates, 'Father of Medicine'
      referred to Elderberry as 'natures medicine chest'.

      In vitro Sambucus Formosana Nakai extract showed potent antiviral activity against human
      coronavirus Netherlands 63 ( NL63) in terms of decreased cytopathic effect and sub-G1 arrest
      in coronavirus infected cells. It produces a significant reduction in viral yield, plaque
      formation and virus attachment. The authors conclude that like Sambucus nigra L., Sambucus
      FormosanaNakai might possess antiviral features against the broad spectrum of human
      respiratory coronaviruses . This supports the previously published data of Sambucus spp., and
      Sambucus nigra L. providing the antiviral properties against influenza A and B viruses and
      herpes simplex type 1 . In 1995 it was demonstrated a significant improvement in symptoms in
      93.3% of patients treated with standardised elderberry extract within 2 days compared to
      within 6 days in the control arm (p<0.001).

      Complete cure occurred in 90% of those receiving the extract in 2 to 3 days . Subsequent
      randomised double -blind studies demonstrated no adverse events and significant improvement
      in clinical symptoms and higher antibody titres in those receiving Sambuci fructus .Chen at
      al 2014 demonstrated with in vitro testing of coronavirus Infectious Bronchitis Virus (IBV)
      with Sambucus.nigra a reduction in virus titres by four orders of magnitude, compromised
      envelopes and membrane vesicles. This virion disruption likely renders it non-infectious . Of
      further interest was that complete inhibition occurred when pre-treatment of virus in
      combination with post- infection treatment.

      SARS-CoV-2 (COVID-19) is a readily transmissible virus that has a wide-ranging incubation
      period of 2-14 days (US Centers for Disease Control and Prevention). The symptoms are often
      non-specific and include fever, cough, fatigue, diarrhoea and loss of sense of taste and
      smell. Clinical features range from mild to severe. Varying transmission patterns and mild
      symptoms are of concern as they facilitate rapid spread. Pre-existing potential drug
      therapies are under investigation, and only started once the patient has symptoms, but do
      have well established side effect profiles. Prophylaxis and prevention are currently
      dependent on social distancing and isolating with vaccines remaining in development,
      potentially not for mass use in the near future.

      Sambucus extract has well documented anti-viral properties and no known drug interactions
      were identified in the literature. Hence, Sambucus maybe well suited for limited prophylaxis
      or treatment of mild/ moderate COVID-19. There is clear in Vitro evidence of activity against
      coronavirus and in human trials of influenza. The aim of this study is to see if Sambucol®
      Black Elderberry Original Liquid (Sambucus nigra) at a dose of 15ml, 4 times a day, reduces
      the duration or severity of symptoms of COVID-19. Symptomatic patients presenting to drive
      through testing (i.e. non-hospitalised) who test positive and who consent will be randomised
      to placebo or Sambucol® and blinded to treatment allocation. Study staff/investigators
      responsible for assessing outcomes and data analysis will also be blinded to treatment
      allocation. Data will be collected to determine resolution of symptoms and the two groups
      compared.
    

Intervention name(s): Sambucol® Black Elderberry Original (Sambucus nigra) Liquid; Placebo for Sambucol® Black Elderberry Original (Sambucus nigra)
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Sambucol® Black Elderberry Original (Sambucus nigra) Liquid has been used as a supplement since 1991 with no reports of adverse effects received by the Manufacturer.; Placebo for Sambucol® Black Elderberry Original (Sambucus nigra) Liquid Constituents: 70% (w/w) of glucose syrup, Flavouring agent: Elderberry Blossom
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study is a superiority test of Sambucol to placebo in the treatment of COVID 19 positive patients, with a parallel design.
Single Centre, placebo controlled, single blinded, two arm, randomised controlled trial.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment