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CompletedNCT03410862Updated Jan 19, 2021Results posted

Evaluating The Safety And Clinical Efficacy Of Elderberry Extract In Patients With Influenza

A Phase 4 interventional study of Elderberry Extract and Placebos in Influenza, Human, sponsored by michael macknin. Completed at 1 site in United States. Open to participants aged 5 Years and older. Per ClinicalTrials.gov, last updated 2021-01-19.

Sponsored by michael macknin · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
87
Allocation
Randomized
Ages
5 Years and older
Sex
All
01

Study summary

This research is being done to determine if an extract of cooked elderberries will help decrease the duration and severity of influenza symptoms in patients with confirmed influenza. Involvement in this study requires an initial patient screening at the time of their Emergency Department visit in order to confirm eligibility for the study. Once patients have been consented and enrolled as a participant, they will be randomized to take by mouth either Elderberry Extract or a placebo (a similar appearing and tasting liquid without elderberry) for a duration of 5 days. Study information regarding medication adherence, body temperature, symptoms, severity of symptoms, and any possible side effects will be collected from daily phone surveys conducted by the study coordinator. Participation in the study will end after at least 5 days once the patient has not had a temperature above 100°F and has had no influenza symptoms for at least 24 hours, or after 21 days in the study, whichever occurs first.

02

Conditions studied

  • Influenza, Human

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Keywords

  • Elderberry
  • Influenza
03

Who can participate

Ages eligible
5 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • With 48 hours or less of an influenza illness documented by polymerase chain reaction
  • Have AT LEAST 2 of the following 7 influenza symptoms (nasal congestion, sore throat, cough, aches and pains, fatigue, headaches, and chills or sweats) graded as either moderate or severe
  • Have access to a phone
  • Subjects are capable of giving informed consent or have an acceptable legally authorized representative capable of giving consent on the subject's behalf with informed assent given by subject.
  • Have been prescribed or offered a prescription for oseltamivir (Tamiflu)

Exclusion criteria

Exclusion Criteria:

  • Known allergy to elderberry extract or oseltamivir
  • Use of antibiotic or antiviral medication on presentation to the study
  • Women who are pregnant, breastfeeding women, or do not agree to appropriate contraception (abstinence, hormonal, intrauterine device, and barrier) to prevent pregnancy during the study.
  • Patients with HIV
  • Patients with cystic fibrosis
  • Patients taking elderberry extract
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
87 participants (actual)

Study arms

  • Experimental
    Elderberry Extract

    Patients will be supplied a liquid Elderberry Extract used to treat their confirmed human influenza. The dosage of the assigned medication will be 15 ml, or 1 tablespoon. Participants aged 5-12 will be asked to take the medication 2 times per day (morning/night) for a period of 5 days. Participants aged 13 and above will be asked to take the medication 4 times per day (morning/noon/afternoon/night) for a period of 5 days.

    Drug: Elderberry Extract

  • Placebo comparator
    Placebo

    Patients will be supplied a liquid Placebo medication (similar in appearance and taste of Elderberry Extract) used to treat their confirmed human influenza. The dosage of the assigned medication will be 15 ml, or 1 tablespoon. Participants aged 5-12 will be asked to take the medication 2 times per day (morning/night) for a period of 5 days. Participants aged 13 and above will be asked to take the medication 4 times per day (morning/noon/afternoon/night) for a period of 5 days.

    Drug: Placebos

Interventions

  • DrugElderberry Extract

    Thick reddish-brown liquid of Sambucus Nigra (Black Elderberry)

    Also known as: Sambucol

  • DrugPlacebos

    Thick reddish-brown liquid similar in appearance and taste to Elderberry Extract not containing elderberry

05

What researchers measure

Primary outcomes

  1. Number of Days Until Alleviation of Flu Symptoms Post Treatment

    Symptoms will be recorded using the scoring system described in a meta-analysis of "all published and unpublished Roche-sponsored randomized placebo-controlled, double-blind trials of oseltamivir treatment in adult influenza" (BMJ 4/9/2014). "The primary outcome will be time to alleviation of all symptoms. Seven influenza symptoms (nasal congestion, sore throat, cough, aches and pains, fatigue, headaches, and chills or sweats)" will be graded by severity as "none/absent" (0), "mild" (1), "moderate" (2), or "severe" (3). Alleviation will be defined to arise when all symptoms scored as absent or mild, and remain so for at least 21.5 hours."

    Time frame: every 24 hours post study drug administration for minimum of 5 days up to 21 days

  2. Number of Days Until Complete Resolution of All Flu Symptoms for 24 Hours

    Participants were called daily and asked to report on the severity of their symptoms present. Symptoms graded according to severity score (NONE/ABSENT=0 MILD=1 MODERATE=2 SEVERE=3).

    Time frame: every 24 hours post study drug administration for minimum of 5 days up to 21 days

06

Results

Posted Jan 19, 2021
Limitations and caveats
Outcomes relied solely on self reports of patients' symptoms. We did not subtype the influenza viruses detected in our study and did not check for virus sensitivity to elderberry and to oseltamivir.

Participant flow

Participant flow — Overall Study
MilestoneElderberry ExtractPlacebo
Started4344
Completed4142
Not completed22

Outcome measures

PrimaryNumber of Days Until Alleviation of Flu Symptoms Post Treatment

Symptoms will be recorded using the scoring system described in a meta-analysis of "all published and unpublished Roche-sponsored randomized placebo-controlled, double-blind trials of oseltamivir treatment in adult influenza" (BMJ 4/9/2014). "The primary outcome will be time to alleviation of all symptoms. Seven influenza symptoms (nasal congestion, sore throat, cough, aches and pains, fatigue, headaches, and chills or sweats)" will be graded by severity as "none/absent" (0), "mild" (1), "moderate" (2), or "severe" (3). Alleviation will be defined to arise when all symptoms scored as absent or mild, and remain so for at least 21.5 hours."

Time frame:
every 24 hours post study drug administration for minimum of 5 days up to 21 days
Reported as:
Mean · days
Number of Days Until Alleviation of Flu Symptoms Post Treatment
daysElderberry ExtractPlacebo
Number of Days Until Alleviation of Flu Symptoms Post Treatment5.3 ± 3.64.9 ± 2.8
PrimaryNumber of Days Until Complete Resolution of All Flu Symptoms for 24 Hours

Participants were called daily and asked to report on the severity of their symptoms present. Symptoms graded according to severity score (NONE/ABSENT=0 MILD=1 MODERATE=2 SEVERE=3).

Time frame:
every 24 hours post study drug administration for minimum of 5 days up to 21 days
Reported as:
Mean · days
Number of Days Until Complete Resolution of All Flu Symptoms for 24 Hours
daysElderberry ExtractPlacebo
Number of Days Until Complete Resolution of All Flu Symptoms for 24 Hours8.6 ± 3.98.7 ± 3.9

Adverse events

Collected over Baseline + 6 months. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Elderberry Extract0/43 (0%)1/43 (2.3%)4/43 (9.3%)
Placebo0/44 (0%)2/44 (4.5%)1/44 (2.3%)
Most frequent serious events
Most frequent serious events
EventElderberry ExtractPlacebo
HospitalizationGeneral disorders1/432/44
Most frequent other events
Most frequent other events
EventElderberry ExtractPlacebo
Dry MouthGeneral disorders4/431/44

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Elderberry ExtractPlaceboTotal
<=18 years161834
Between 18 and 65 years272653
>=65 years000
Sex: Female, Male
Sex: Female, Male(Participants)Elderberry ExtractPlaceboTotal
Female162238
Male272249
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Elderberry ExtractPlaceboTotal
American Indian or Alaska Native000
Asian101
Native Hawaiian or Other Pacific Islander000
Black or African American151631
White272047
More than one race000
Unknown or Not Reported088
Region of Enrollment
Region of Enrollment(participants)Elderberry ExtractPlaceboTotal
United States434487
07

Study locations

1 site
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
08

References and documents

Publications

  • Macknin M, Wolski K, Negrey J, Mace S. Elderberry Extract Outpatient Influenza Treatment for Emergency Room Patients Ages 5 and Above: a Randomized, Double-Blind, Placebo-Controlled Trial. J Gen Intern Med. 2020 Nov;35(11):3271-3277. doi: 10.1007/s11606-020-06170-w. Epub 2020 Sep 14. PubMed 32929634 ↗

Study documents

  • Protocol and statistical analysis plan · Nov 8, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — No plan to share data, needs HIPPA clearance and specific IRB approval, we did not plan on original data being shared

09

Registry details

Key details

Study ID
NCT03410862
Lead sponsor
michael macknin
Collaborators
Pharmacare Laboratories
Responsible party
michael macknin (Staff Physician, The Cleveland Clinic) — Sponsor-investigator
First posted
Jan 25, 2018
Start date
Jan 29, 2018
Primary completion
Jun 25, 2019
Completion
Jun 25, 2019
Results posted
Jan 19, 2021
Last update
Jan 19, 2021

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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