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

• Sponsor: michael macknin (Other)
• Overall Status: Completed
• CT.gov ID: NCT03410862
• Collaborator: Pharmacare Laboratories (Other)
• Enrollment: 87
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.8
• Patients Per Site Per Month: 5.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Influenza, Human	Drug: Elderberry Extract; Drug: Placebos	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase IV Study Evaluating The Safety And Clinical Efficacy Of Elderberry Extract In Patients With Influenza: A Randomized, Double-Blind Placebo-Controlled Trial
• Actual Study Start Date: Jan 29, 2018
• Actual Primary Completion Date: Jun 25, 2019
• Actual Study Completion Date: Jun 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
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; Thick reddish-brown liquid of Sambucus Nigra (Black Elderberry); Other Names: Sambucol
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; Thick reddish-brown liquid similar in appearance and taste to Elderberry Extract not containing elderberry

Outcome Measures

Primary Outcome Measures

1. Number of Days Until Alleviation of Flu Symptoms Post Treatment [every 24 hours post study drug administration for minimum of 5 days up to 21 days]

   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."

2. Number of Days Until Complete Resolution of All Flu Symptoms for 24 Hours [every 24 hours post study drug administration for minimum of 5 days up to 21 days]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years and Older
• Sexes Eligible for Study: 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:

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• michael macknin
• Pharmacare Laboratories

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 8, 2018

More Information

Publications

None provided.

• Responsible Party: michael macknin, Staff Physician, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT03410862
• Other Study ID Numbers: 17-1682
• First Posted: Jan 25, 2018
• Last Update Posted: Jan 19, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by michael macknin, Staff Physician, The Cleveland Clinic: Elderberry; Influenza
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Arm/Group Title	Elderberry Extract	Placebo
Arm/Group Description	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. Elderberry Extract: Thick reddish-brown liquid of Sambucus Nigra (Black Elderberry)	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. Placebos: Thick reddish-brown liquid similar in appearance and taste to Elderberry Extract not containing elderberry
Period Title: Overall Study
STARTED	43	44
COMPLETED	41	42
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Elderberry Extract	Placebo	Total
Arm/Group Description	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. Elderberry Extract: Thick reddish-brown liquid of Sambucus Nigra (Black Elderberry)	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. Placebos: Thick reddish-brown liquid similar in appearance and taste to Elderberry Extract not containing elderberry	Total of all reporting groups
Overall Participants	43	44	87
Age (Count of Participants)
<=18 years	16 37.2%	18 40.9%	34 39.1%
Between 18 and 65 years	27 62.8%	26 59.1%	53 60.9%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	16 37.2%	22 50%	38 43.7%
Male	27 62.8%	22 50%	49 56.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.3%	0 0%	1 1.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	15 34.9%	16 36.4%	31 35.6%
White	27 62.8%	20 45.5%	47 54%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	8 18.2%	8 9.2%
Region of Enrollment (participants) [Number]
United States	43 100%	44 100%	87 100%

Outcome Measures

1. Primary Outcome

Title	Number of Days Until Alleviation of Flu Symptoms Post Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Elderberry Extract	Placebo
Arm/Group Description	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. Elderberry Extract: Thick reddish-brown liquid of Sambucus Nigra (Black Elderberry)	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. Placebos: Thick reddish-brown liquid similar in appearance and taste to Elderberry Extract not containing elderberry
Measure Participants	43	44
Mean (Standard Deviation) [days]	5.3 (3.6)	4.9 (2.8)

2. Primary Outcome

Title	Number of Days Until Complete Resolution of All Flu Symptoms for 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Elderberry Extract	Placebo
Arm/Group Description	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. Elderberry Extract: Thick reddish-brown liquid of Sambucus Nigra (Black Elderberry)	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. Placebos: Thick reddish-brown liquid similar in appearance and taste to Elderberry Extract not containing elderberry
Measure Participants	43	44
Mean (Standard Deviation) [days]	8.6 (3.9)	8.7 (3.9)

Adverse Events

Time Frame	Baseline + 6 months
Arm/Group Title	Elderberry Extract		Placebo
Arm/Group Description	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. Elderberry Extract: Thick reddish-brown liquid of Sambucus Nigra (Black Elderberry)		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. Placebos: Thick reddish-brown liquid similar in appearance and taste to Elderberry Extract not containing elderberry
All Cause Mortality
	Elderberry Extract		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		0/44 (0%)
Serious Adverse Events
	Elderberry Extract		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/43 (2.3%)		2/44 (4.5%)
General disorders
Hospitalization	1/43 (2.3%)	1	2/44 (4.5%)	2
Other (Not Including Serious) Adverse Events
	Elderberry Extract		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/43 (9.3%)		1/44 (2.3%)
General disorders
Dry Mouth	4/43 (9.3%)	4	1/44 (2.3%)	1

Limitations/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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.