Cerebrolycin for Treatment of Covid-related Anosmia and Ageusia

Sponsor

Assiut University (Other)

Overall Status

Completed

CT.gov ID

NCT04830943

Collaborator

(none)

100

Enrollment

Location

Arm

7.9

Actual Duration (Months)

12.6

Patients Per Site Per Month

Study Details

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

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 :

Aug 1, 2020

Actual Primary Completion Date :

Feb 28, 2021

Actual Study Completion Date :

Mar 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Other: 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 Names: Neurotropic factors

Arm

Intervention/Treatment

Other: 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 Names:

Neurotropic factors

Outcome Measures

Primary Outcome Measures

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. [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

The short modified version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS) [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).
The Globas Rating for smell (GRS) [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
The Globas Rating for taste (GRT) [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

Criteria

Ages Eligible for Study:

20 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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