Efficacy of a Carrageenan nasal spray in patients with common cold: a randomized controlled trial

Respiratory Research

Christian A Mueller²  Thomas Lion⁴  Andreas Grassauer⁵  Eva Prieschl-Grassauer⁵  Kurt Neumann¹  Angelika Bodenteich⁵  Margit Rauch³  Sven Schneider²  Elisabeth Enzenhofer²  Martin Ludwig² 

[1]E. I. S. Executive Information Service GmbH, Mariahilfer Straße 88a/1/5, 1070 Vienna, Austria

[2]Department of Otorhinolaryngology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria

[3]Children’s Cancer Research Institute and LabDia Labordiagnostik, Zimmermannplatz 8, 1090 Vienna, Austria

[4]Department of Pediatrics, Medical University of Vienna, Waehringer Guertel, 18-20, 1090 Vienna, Austria

[5]Marinomed Biotechnologie GmbH, Veterinaerplatz 1, 1210 Vienna, Austria

关键词: Carrageenan;    Disease;    Respiratory;    Virus;    Common cold;   

Others  :  792344
DOI  :  10.1186/1465-9921-14-124

 received in 2013-08-01, accepted in 2013-11-10,  发布年份 2013

【 摘 要 】

Background

The common cold is the most widespread viral infection in humans. Iota-carrageenan has previously shown antiviral effectiveness against cold viruses in clinical trials. This study investigated the efficacy of a carrageenan-containing nasal spray on the duration of the common cold and nasal fluid viral load in adult patients.

Methods

In a randomized, double-blind, placebo-controlled trial, 211 patients suffering from early symptoms of the common cold were treated for seven days. Application was performed three times daily with either a carrageenan-supplemented nasal spray or saline solution as placebo with an overall observation period of 21 days. The primary endpoint was the duration of disease defined as the time until the last day with symptoms followed by all other days in the study period without symptoms. During the study, but prior unblinding, the definition of disease duration was adapted from the original protocol that defines disease duration as the time period of symptoms followed by 48 hours without symptoms.

Results

In patients showing a laboratory-confirmed cold virus infection and adherence to the protocol, alleviation of symptoms was 2.1 days faster in the carrageenan group in comparison to placebo (p = 0.037). The primary endpoint that had been prespecified but was changed before unblinding was not met. Viral titers in nasal fluids showed a significantly greater decrease in carrageenan patients in the intention-to-treat population (p = 0.024) and in the per protocol population (p = 0.018) between days 1 and 3/4.

Conclusions

In adults with common cold virus infections, direct local administration of carrageenan with nasal sprays reduced the duration of cold symptoms. A significant reduction of viral load in the nasal wash fluids of patients confirmed similar findings from earlier trials in children and adults.

Trial registration

Current Controlled Trials ISRCTN80148028

【 授权许可】

   
2013 Ludwig et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Fendrick AM, Monto AS, Nightengale B, Sarnes M: The economic burden of non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med 2003, 163:487-494.
• [2]Bertino JS: Cost burden of viral respiratory infections: issues for formulary decision makers. Am J Med 2002, 112(Suppl 6A):42S-49S.
• [3]Fox JP, Hall CE, Cooney MK, Luce RE, Kronmal RA: The seattle virus watch. II. Objectives, study population and its observation, data processing and summary of illnesses. Am J Epidemiol 1972, 96:270-285.
• [4]Monto AS, Ullman BM: Acute respiratory illness in an American community. The tecumseh study. JAMA 1974, 227:164-169.
• [5]Gwaltney JMJ, Hendley JO, Simon G, Jordan WS Jr: Rhinovirus infections in an industrial population. I. The occurrence of illness. N Engl J Med 1966, 275:1261-1268.
• [6]Makela MJ, Puhakka T, Ruuskanen O, Leinonen M, Saikku P, Kimpimaki M, Blomqvist S, Hyypia T, Arstila P: Viruses and bacteria in the etiology of the common cold. J Clin Microbiol 1998, 36:539-542.
• [7]Fendrick AM: Viral respiratory infections due to rhinoviruses: current knowledge, new developments. Am J Ther 2003, 10:193-202.
• [8]Snell NJ: New treatments for viral respiratory tract infections–opportunities and problems. J Antimicrob Chemother 2001, 47:251-259.
• [9]Barrett B, Brown R, Rakel D, Mundt M, Bone K, Barlow S, Ewers T: Echinacea for treating the common cold: a randomized trial. Ann Intern Med 2010, 153:769-777.
• [10]Josling P: Preventing the common cold with a garlic supplement: a double-blind, placebo-controlled survey. Adv Ther 2001, 18:189-193.
• [11]Karlowski TR, Chalmers TC, Frenkel LD, Kapikian AZ, Lewis TL, Lynch JM: Ascorbic acid for the common cold. A prophylactic and therapeutic trial. JAMA 1975, 231:1038-1042.
• [12]Sasazuki S, Sasaki S, Tsubono Y, Okubo S, Hayashi M, Tsugane S: Effect of vitamin C on common cold: randomized controlled trial. Eur J Clin Nutr 2006, 60:9-17.
• [13]Meydani SN, Leka LS, Fine BC, Dallal GE, Keusch GT, Singh MF, Hamer DH: Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. JAMA 2004, 292:828-836.
• [14]Graat JM, Schouten EG, Kok FJ: Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA 2002, 288:715-721.
• [15]Prasad AS, Beck FW, Bao B, Snell D, Fitzgerald JT: Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, and adhesion molecules in patients with common cold treated with zinc acetate. J Infect Dis 2008, 197:795-802.
• [16]Douglas RM, Hemila H, Chalker E, Treacy B: Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2007. doi:10.1002/14651858.CD000980.pub3
• [17]Linde K, Barrett B, Wolkart K, Bauer R, Melchart D: Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev 2006. doi:10.1002/14651858.CD000530.pub2
• [18]Lissiman E, Bhasale AL, Cohen M: Garlic for the common cold. Cochrane Database Syst Rev 2012. doi:10.1002/14651858.CD006206.pub3
• [19]Wu T, Zhang J, Qiu Y, Xie L, Liu GJ: Chinese medicinal herbs for the common cold. Cochrane Database Syst Rev 2007. doi:10.1002/14651858.CD004782.pub2
• [20]Hemila H, Virtamo J, Albanes D, Kaprio J: The effect of vitamin E on common cold incidence is modified by age, smoking and residential neighborhood. J Am Coll Nutr 2006, 25:332-339.
• [21]De Sutter AI, Van Driel ML, Kumar AA, Lesslar O, Skrt A: Oral antihistamine-decongestant-analgesic combinations for the common cold. Cochrane Database Syst Rev 2012. doi:10.1002/14651858.CD004976.pub3
• [22]Kim SY, Chang YJ, Cho HM, Hwang YW, Moon YS: Non-steroidal anti-inflammatory drugs for the common cold. Cochrane Database Syst Rev 2009. doi:10.1002/14651858.CD006362.pub2
• [23]Gonzalez ME, Alarcon B, Carrasco L: Polysaccharides as antiviral agents: antiviral activity of carrageenan. Antimicrob Agents Chemother 1987, 31:1388-1393.
• [24]Maguire RA, Zacharopoulos VR, Phillips DM: Carrageenan-based nonoxynol-9 spermicides for prevention of sexually transmitted infections. Sex Transm Dis 1998, 25:494-500.
• [25]Obiero J, Mwethera PG, Wiysonge CS: Topical microbicides for prevention of sexually transmitted infections. Cochrane Database Syst Rev 2012. doi:10.1002/14651858.CD007961.pub2
• [26]Leibbrandt A, Meier C, König-Schuster M, Weinmüllner R, Kalthoff D, Pflugfelder B, Graf P, Frank-Gehrke B, Beer M, Fazekas T, et al.: Iota-carrageenan is a potent inhibitor of influenza A virus infection. PLoS One 2010. doi:10.1371/journal.pone.0014320
• [27]Grassauer A, Weinmüllner R, Meier C, Pretsch A, Prieschl-Grassauer E, Unger H: Iota-Carrageenan is a potent inhibitor of rhinovirus infection. Virol J 2008. doi:10.1186/1743-422X-5-107
• [28]Eccles R, Meier C, Jawad M, Weinmüllner 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. doi:10.1186/1465-9921-11-108
• [29]Fazekas T, Eickhoff P, Pruckner N, Vollnhofer G, Fischmeister G, Diakos C, Rauch M, Verdianz M, Zoubek A, Gadner H, et al.: Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold. BMC Complement Altern Med 2012. doi:10.1186/1472-6882-12-147
• [30]Jackson GG, Dowling HF, Spiesman IG, Boand AV: Transmission of the common cold to volunteers under controlled conditions. I. The common cold as a clinical entity. AMA Arch Intern Med 1958, 101:267-278.
• [31]Neumann K: The signal strengthening power of statistics: a demonstration of regression with unknown model domain in statistics and pharmacoeconomics. Pharmacoepidemiol Drug Saf 1997, 6(Suppl 3):S27-S29.
• [32]Kassel JC, King D, Spurling GKP: Saline nasal irrigation for acute upper respiratory tract infections (Review). Cochrane Database Syst Rev 2010. doi:10.1002/14651858.CD006821.pub2
• [33]Gwaltney JMJ, Hendley JO, Patrie JT: Symptom severity patterns in experimental common colds and their usefulness in timing onset of illness in natural colds. Clin Infect Dis 2003, 36:714-723.
• [34]Gwaltney JMJ, Buier RM, Rogers JL: The influence of signal variation, bias, noise and effect size on statistical significance in treatment studies of the common cold. Antiviral Res 1996, 29:287-295.
• [35]Claude JA, Grimm A, Savage HP, Pinkerton KE: Perinatal exposure to environmental tobacco smoke (ETS) enhances susceptibility to viral and secondary bacterial infections. Int J Environ Res Public Health 2012, 9:3954-3964.
• [36]Grigg J, Walters H, Sohal SS, Wood-Baker R, Reid DW, Xu CB, Edvinsson L, Morissette MC, Stampfli MR, Kirwan M, et al.: Cigarette smoke and platelet-activating factor receptor dependent adhesion of Streptococcus pneumoniae to lower airway cells. Thorax 2012, 67:908-913.