Cerebrolycin for Treatment of Covid-related Anosmia and Ageusia

• ClinicalTrials.gov Identifier: NCT04830943
• Recruitment Status: Completed
• First Posted: April 5, 2021
• Last Update Posted: April 5, 2021
• Sponsor: Assiut University
• Information provided by (Responsible Party): Sherifa Ahmed Hamed, Assiut University

Study Description

Brief Summary:

The loss of smell and taste is a prominent symptom of COVID-19. Studies found that patterns of smell loss due to Covid-19 infection differ from that of other respiratory viruses being much more profound in the Covid-19 patents and did not associate with runny, congested, or blocked-up nose. The researchers suggest that smell and taste testing can be used for fast COVID-19 screening. Studies found that the Covid-19 virus has similarities with severe acute respiratory syndrome coronavirus (SARS-CoV), which has been reported to enter the brain, via smell receptors in the nose. The sudden onset and relatively fast recovery in some patients suggest that COVID-19 anosmia is not caused by damage to the central nervous system but rather by the loss of smell information before it gets to the brain (smell receptors). They also found that it has different behavior from other respiratory viruses as it causes over-reaction of the immune system (or a cytokine storm). Trials to treat post-COVID anosmia using local steroid applications, sniffing of strong odors or scents or use of different vitamins (for several weeks to months) did not provide rapid, satisfactory or even significant recovery of olfactory dysfunction. Fortunately, the olfactory neurons can regenerate, however, studies reported variable prognoses, some patients recovered within weeks which others may have persistent deficits for months or even a year. In this study, the researchers hypothesize that cerebrolysin, a drug of neurotrophic and neuroprotective properties, can be used to treat patients with persistent post-COVID anosmia or ageusia or promote functional recovery of smell and taste deficits.

Condition or disease	Intervention/treatment	Phase
Covid19 Related Anosmia and Aguesia	Drug: Cerebrolysin	Phase 4

Detailed Description:

Initial descriptions of the COVID-19 pandemic have focused on its acute severe manifestations. After several months, data have emerged about the mild disease and Post-COVID syndrome. The diminished senses of smell (or hyposmia/anosmia) and taste (or hypogeusia/ageusia) have been commonly reported in the pandemic. Hyposmia/anosmia and hypogeusia/ageusia have also been reported with previous coronaviruses. In late March, the professional society of Ear, Nose, and Throat (ENT) in the United Kingdom (UK) published an advisory on evidence from South Korea, China, and Italy that significant number of COVID-19 positive patients also lost smell and/or taste. Based also on several other reports which reported that 66-88% of patients have lost smell and/or taste due to COVID-19 infection, the American Academy of Otolaryngology-Head and Neck Surgery and World Health Organization (WHO) have added anosmia and ageusia to the list of symptoms of COVID-19. The prognosis of such deficits seems variable. Some reported recovery within few weeks; while many reported persistence of deficits for several months or even more than a year after the onset of the condition. Furthermore, some patients developed respiratory symptoms later after anosmia while others remained asymptomatic. The exact mechanisms for these deficits are still under research. In animal models, the investigators found that coronaviruses could impair the olfactory neuroepithelium through the expression of angiotensin-converting enzyme type 2 (ACE2) in the sustentacular cells or damage the receptors. Treatment trials of post-COVID anosmia included the application of nasal corticosteroids, regular sniffing of different odors and strong scents, and treatment with antioxidants and vitamins. However, none was therapeutically effective. Previous preclinical and clinical studies have shown that treatment with neurotrophic polypeptides can promote neurological recovery for many neurodegenerative and acquired nervous system diseases. As the olfactory neurons are capable of regeneration, the researchers propose that treating patients with prolonged post-COVID anosmia or ageusia with cerebrolysin, a drug of neurotrophic and neuroprotective properties may promote recovery of olfactory and gustatory dysfunctions. Cerebrolysin is a mixture of peptides purified from pig brains, including (and not limited to) brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effectiveness of Cerebrolycin for Treatment of Post-covid Olfactory and Gustatory Dysfunctions: A Pilot Study
• Actual Study Start Date: August 1, 2020
• Actual Primary Completion Date: February 28, 2021
• Actual Study Completion Date: March 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Olfactory and gustatory disorders after covid 19 infection; Cerebrolysin Dose:10 ml ampoule (1ml contains 215.2 mg cerebrolysin) once daily through intramuscular injection five times per week, for a total of 20 treatments (for 4 weeks), after which the cycle was repeated again for at least 8 more weeks.	Drug: Cerebrolysin; Cerebrolysin will be prescribed in a dose of 10 ml ampoule once daily through intramuscular injection (1ml contains 215.2 mg cerebrolysin) for five times per week, for a total of 20 treatments (for 4 weeks), after which the cycle was repeated again for at least 8 more weeks.; Other Name: Neurotropic factors

Outcome Measures

Primary Outcome Measures :

1. The smell and taste questionnaire component of the National Health and Nutrition Examination Survey (NHNES). And the modified Arabic translated and validated sniffin' sticks odor identification test was used for objective olfactory evaluations. [ Time Frame: The within subject change in sniffin' sticks test between baseline and 12- and -24 assessment time frame ]
   The NHNES questions have been selected to characterize the variation, timing and associated-symptoms of both olfactory and gustatory systems. sniffin' sticks odor identification test, a total of 16 scents were presented via a pen device to patients for 3 seconds followed by a forced choice from 4 given options with a total possible score of 16 points. According to the results, patients were classified as normosmic (score between 12-16), hyposmic (score between 9-11) or anosmic (score 8 or below). The increase in at least 4 points from baseline indicates a clinically meaningful improvement. sniffin' sticks odor identification test has high internal reliability across a wide range of population.

Secondary Outcome Measures :

1. The short modified version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS) [ Time Frame: The within subject chage in QOD-NS between baseline and assessment frame ]
   sQOD-NS is a seven-item patient-reported outcome questionnaire including social, eating, annoyance, and anxiety questions. Each item is rated on a scale of 0-3, with higher scores reflecting better olfactory-specific QOL. The total score ranges from 0 (severe impact on QoL) to 21 (no impact on QoL).
2. The Globas Rating for smell (GRS) [ Time Frame: 6 weeks, 12 weeks, 18 weeks and 24 weeks ]
   GRS is a single-item, global rating that asks the patient to rate his current sense of smell as follow: excellent, very good, good, fair, poor or absent
3. The Globas Rating for taste (GRT) [ Time Frame: 6 weeks, 12 weeks, 18 weeks and 24 weeks ]
   GRT is a single-item, global rating that asks the patient to rate his current sense of taste as follow: excellent, very good, good, fair, poor or absent

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• A random sample of at least 100 adults with sudden hyposmia/anosmia and/or hypoageusia/ageusia during COVID-19 pandemics which persist till the onset of the study. Persisting symptoms were defined by the presence at day 30 or day 60 of anosmia/ageusia.
• Patients who experienced persistent olfactory and/or smell manifestations after recovery from their initial acute COVID-19 illness.

Exclusion Criteria:

• Prior neurologic, medical or psychiatric disease.
• Other known infection at onset
• Nasal congestion
• Nasal polyps
• Surgery or head trauma or radiation for head and neck cancers as may result in injury to the nerves that control smell
• Exposure to toxic chemicals (such as pesticides and solvents)
• Cocaine or other drug abuse

Contacts and Locations

Locations

Egypt

Assiut University Hospitals, Faculty of Medicine

Assiut, Egypt, 71516

Sponsors and Collaborators

Assiut University

Investigators

• Principal Investigator: Sherifa A Hamed, M.D.; Assiut University, Faculty of Medicine

More Information

Publications of Results:

Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C, Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, Ris L, Lovato A, De Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020 Aug;277(8):2251-2261. doi: 10.1007/s00405-020-05965-1. Epub 2020 Apr 6.

Other Publications:

Chachkhiani D, Soliman MY, Barua D, Isakadze M, Villemarette-Pittman NR, Devier DJ, Lovera JF. Neurological complications in a predominantly African American sample of COVID-19 predict worse outcomes during hospitalization. Clin Neurol Neurosurg. 2020 Oct;197:106173. doi: 10.1016/j.clineuro.2020.106173. Epub 2020 Aug 25.

Shrestha GS, Khanal S, Sharma S, Nepal G. COVID-19: Current Understanding of Pathophysiology. J Nepal Health Res Counc. 2020 Nov 13;18(3):351-359. doi: 10.33314/jnhrc.v18i3.3028.

Veinbergs I, Mante M, Mallory M, Masliah E. Neurotrophic effects of Cerebrolysin in animal models of excitotoxicity. J Neural Transm Suppl. 2000;59:273-80.

• Responsible Party: Sherifa Ahmed Hamed, Professor of Neurology, Assiut University
• ClinicalTrials.gov Identifier: NCT04830943
• Other Study ID Numbers: COVID-NGF/AUH_SAH/2020
• First Posted: April 5, 2021
• Last Update Posted: April 5, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sherifa Ahmed Hamed, Assiut University:

COVID-19; ; anosmia; ; ageusia; ; cerebrolysin

Additional relevant MeSH terms:

COVID-19; Anosmia; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Olfaction Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Cerebrolysin; Neuroprotective Agents; Protective Agents; Physiological Effects of Drugs; Nootropic Agents