Carrageenan Nasal Spray for COVID-19 Prophylaxis

NCT04590365 | Completed DMC

• 1 other identifier: 283187
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 1

Brief Summary

The current COVID-19 pandemic is the biggest global healthcare challenge in the last century, and the number of cases in the next 12 months is likely to increase. There is currently no proven treatment, chemoprophylaxis or vaccine against COVID-19, which exhibits a wide clinical spectrum from asymptomatic carriage to mild upper respiratory tract infection, severe viral pneumonia to acute respiratory distress syndrome and death. Key workers are at high risk of exposure highlighting the need for effective preventative strategies. SARS-CoV-2 is a positive-sense single-stranded enveloped RNA virus which transmits via droplets, aerosols and direct contact, to reach their target naso- and oropharyngeal epithelial cells through initial electrostatic interactions to cell surface heparan sulphate (HS) proteoglycans. Carrageenan mimics cell surface HS, thereby trapping the virus to allow mucociliary clearance and has demonstrated anti-viral activity in-vitro and in a number of common cold clinical trials when administered as a nasal spray. ICE-COVID a randomised, double blind, placebo-controlled phase III trial of the prophylactic efficacy of iota-carrageenan nasal and throat spray in preventing COVID-19 illness in at risk healthcare professionals. Participants (n=240) will be randomly allocated to either the treatment arm (verum Coldamaris plus, 0.12% iota-carrageenan plus 0.04% Kappa-Carrageenan in 0.5% saline) or placebo (Coldamaris sine, saline 0.5%) arm. The study's primary objective is the prevention of COVID-19 infection, confirmed by PCR swab or documented seroconversion. Secondary objectives are to determine if carrageenan sprays reduce the clinical severity of COVID-19 and symptomatic acute respiratory infection of other aetiologies (non-SARS-CoV-2).

Conditions

COVID-19; SARS-CoV 2

Keywords

Carrageenan; Nasal spray; Anti-viral; Prevention; Carragelose

Outcome Measures

Primary Outcomes (1)

• Rate of COVID-19 infection

  Acquisition of COVID-19 infection as confirmed by positive PCR swab taken at the time of symptom onset or positive serology measured 2 weeks after symptom onset or seroconversion at the end of the trial (via trial entry and exit serology) to detect asymptomatic infection during the study period

  9-12 months

Secondary Outcomes (4)

• Duration of COVID-19 infection

  9-12 months

• Hospitalisation due to COVD-19 infection

  9-12 months

• Severity of COVID-19 infection

  9-12 months

• Quality of life of nasal spray use

  9-12 months

Study Arms (2)

Coldamaris plus

EXPERIMENTAL

verum Coldamaris plus i.e. 0.12% Iota-Carrageenan plus 0.04% Kappa-Carrageenan in 0.5% saline

Device: Carrageenan nasal and throat spray

Coldamaris sine

PLACEBO COMPARATOR

Coldamaris sine i.e. 0.5% saline

Device: Saline nasal and throat spray

Interventions

Carrageenan nasal and throat spray DEVICE

Iota-carrageenan nasal and throat spray (verum Coldamaris plus i.e. Iota-Carrageenan 0.12% plus 0.04% Kappa-Carrageenan in 0.5% saline)

Coldamaris plus

Saline nasal and throat spray DEVICE

Saline nasal and throat spray (placebo Coldamaris sine i.e. 0.5% saline)

Coldamaris sine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years;
• Study participants who have given informed consent, and received a copy of signed consent form prior to any study related procedures;
• Healthcare professionals (nurses, doctors, allied health professionals, health care assistants, operating department practitioners) working in Swansea Bay University Health Board initially as well as any other volunteers \>18 years who have not previously tested positive for COVID19 or been vaccinated.
• Subjects agree to refrain from taking over the counter products intended to prevent, intervene in, or treat colds/flu, starting at study entry and continuing through week 10 of the study.

You may not qualify if:

• Capacity, consent and conflicts of interest:
• The person lacks capacity;
• The subject is related to any study personnel or has any other close ties or conflicts of interest with the research team or the study sponsor;
• The subject has received any investigational drug or participated in a clinical trial within 4 weeks of entry to this study.
• Unable to complete the daily symptom tracker
• Unable to communicate in English or Welsh
• Comorbidities:
• Known hypersensitivity or allergy to any component of the test product;
• Severe nasal septal deviation, nasal polyps or other non-infectious condition that could cause nasal obstruction;
• A history of any nasal or sinus surgery in the past that in the opinion of the investigator may influence the symptoms or spray administration;
• An unrelated infection that in the opinion of the investigator may influence symptoms (gastrointestinal infection, other viral diseases such as measles, mumps);
• COVID-19 Status:
• Participants with proven COVID-19 infection (previous positive serology and/or viral PCR swab)
• Participants that have already received their vaccination or already booked in for their vaccination
• Medications:

Sponsors & Collaborators

• Swansea University: lead
• Cardiff University: collaborator
• Marinomed Biotech AG: collaborator
• Walgreens Boots Alliance: collaborator
• Abertawe Bro Morgannwg University Health Board: collaborator

Study Sites (1)

Joint Clinical Research Facility

Swansea, SA6 6NL, United Kingdom

Location

Related Publications (9)

• Buck CB, Thompson CD, Roberts JN, Muller M, Lowy DR, Schiller JT. Carrageenan is a potent inhibitor of papillomavirus infection. PLoS Pathog. 2006 Jul;2(7):e69. doi: 10.1371/journal.ppat.0020069.

  PMID: 16839203 BACKGROUND

• Eccles R, Meier C, Jawad M, Weinmullner R, Grassauer A, Prieschl-Grassauer E. Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold. Respir Res. 2010 Aug 10;11(1):108. doi: 10.1186/1465-9921-11-108.

  PMID: 20696083 BACKGROUND

• Eccles R, Winther B, Johnston SL, Robinson P, Trampisch M, Koelsch S. Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial. Respir Res. 2015 Oct 5;16:121. doi: 10.1186/s12931-015-0281-8.

  PMID: 26438038 BACKGROUND

• Gonzalez ME, Alarcon B, Carrasco L. Polysaccharides as antiviral agents: antiviral activity of carrageenan. Antimicrob Agents Chemother. 1987 Sep;31(9):1388-93. doi: 10.1128/AAC.31.9.1388.

  PMID: 2823697 BACKGROUND

• Grassauer A, Weinmuellner R, Meier C, Pretsch A, Prieschl-Grassauer E, Unger H. Iota-Carrageenan is a potent inhibitor of rhinovirus infection. Virol J. 2008 Sep 26;5:107. doi: 10.1186/1743-422X-5-107.

  PMID: 18817582 BACKGROUND

• Ludwig M, Enzenhofer E, Schneider S, Rauch M, Bodenteich A, Neumann K, Prieschl-Grassauer E, Grassauer A, Lion T, Mueller CA. Efficacy of a carrageenan nasal spray in patients with common cold: a randomized controlled trial. Respir Res. 2013 Nov 13;14(1):124. doi: 10.1186/1465-9921-14-124.

  PMID: 24219370 BACKGROUND

• Leibbrandt A, Meier C, Konig-Schuster M, Weinmullner R, Kalthoff D, Pflugfelder B, Graf P, Frank-Gehrke B, Beer M, Fazekas T, Unger H, Prieschl-Grassauer E, Grassauer A. Iota-carrageenan is a potent inhibitor of influenza A virus infection. PLoS One. 2010 Dec 14;5(12):e14320. doi: 10.1371/journal.pone.0014320.

  PMID: 21179403 BACKGROUND

• Shao Q, Guo Q, Xu Wp, Li Z, Zhao Tt. Specific Inhibitory Effect of kappa-Carrageenan Polysaccharide on Swine Pandemic 2009 H1N1 Influenza Virus. PLoS One. 2015 May 13;10(5):e0126577. doi: 10.1371/journal.pone.0126577. eCollection 2015.

  PMID: 25969984 BACKGROUND

• Jessop ZM, Gibson J, Lim JY, Jovic TH, Combellack E, Dobbs TD, Carter K, Hiles S, Islam S, Healy B, Humphreys I, Eccles R, Hutchings HA, Whitaker IS. A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis-ICE-COVID. Trials. 2022 Sep 15;23(1):782. doi: 10.1186/s13063-022-06685-z.

  PMID: 36109791 DERIVED

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Zita M Jessop, MBBChir PhD

  Swansea University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Allocation to each group, treatment or placebo administration and data analysis will be blinded to both participant and investigator. The sprays will be blinded at the site of manufacture. Trial sealed envelopes will be available in case of any adverse reactions.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study design consists of a double blind, randomised placebo-controlled trial. Of the 480 participants recruited, 240 participants will be randomly allocated to each of either the treatment arm (verum Coldamaris plus i.e. Iota-Carrageenan 0.12% plus 0.04% Kappa-Carrageenan in 0.5% saline) or placebo (Coldamaris sine i.e. 0.5% saline) arms.

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: October 19, 2020
• Study Start: December 17, 2020
• Primary Completion: November 18, 2022
• Study Completion: November 18, 2022
• Last Updated: April 28, 2023

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)