Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05489770 |
| Other study ID # |
2020/COVID19/11 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 5, 2021 |
| Est. completion date |
May 16, 2022 |
Study information
| Verified date |
August 2022 |
| Source |
East Kent Hospitals University NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
