Cerebrolycin for Treatment of Covid-related Anosmia and Ageusia

December 29, 2022 updated by: Sherifa Ahmed Hamed, Assiut University

The Effectiveness of Cerebrolycin, a Multi-modal Neurotrophic Factor, for Treatment of Post-covid-19 Persistent Olfactory, Gustatory and Trigeminal Chemosensory Dysfunctions: A Pilot Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 or interventions as olfactory training. 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 due to different causes. As the olfactory neurons are capable of regeneration, the researchers propose that treating patients with prolonged post-COVID anosmia or ageusia using cerebrolysin, a drug of neurotrophic and neuroprotective properties may promote recovery of olfactory and gustatory dysfunctions. Cerebrolysin is a mixture of peptides purified from 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 Type

Interventional

Enrollment (Actual)

250

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Assiut, Egypt, 71516
        • Assiut University Hospitals, Faculty of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • A random sample of at least 250 adults with sudden hyposmia/anosmia and/or hypoageusia/ageusia during COVID-19 pandemics and experienced persistent olfactory and/or gustatory manifestations after recovery from other acute viral manifestations.
  • compliance for drug intervention (group 1) or olfactory training (group 2) for at least 8 weeks.

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Olfactory and gustatory disorders after covid 19 infection (n = 150)
Cerebrolysin Dose:5 ml ampoule (1ml contains 215.2 mg cerebrolysin) once daily through intramuscular injection five times per week, for a total of 40 treatments (for at least 8 weeks after presentation), after which the cycle was repeated again according to the each patient response to therapy for a maximum of 24 weeks.
Drug: Cerebrolysin
Cerebrolysin will be prescribed in a dose of 5 ml ampoule once daily through intramuscular injection (1ml contains 215.2 mg cerebrolysin) for five times per week, for a total of 40 treatments (for 8 weeks), after which the cycle was individually repeated according to the response of the patient to therapy for a maximum of 24 weeks
Other Names:
  • Neurotropic factors
No Intervention: control group (n = 100)
no drug intervention, just olfactory training using at least 4 strong odors to smell twice daily for at least 15 minutes (every time), for at least 8 weeks after presentation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 subject smell and taste sensations at baseline (presentation)
The NHNES questions have been selected to characterize the variation, timing and associated-symptoms of both olfactory and gustatory systems.
The subject smell and taste sensations at baseline (presentation)
objective testings: sniffen's odor, taste and flavor identification testing
Time Frame: at presentation (baseline)

For quantitative assessment of smell, we used 16 odors familiar to Egyptians For quantitative assessment of taste loss, we used sugar (sweet), salt (salty), lemon (sour), old rumi cheese chips (umami) and coffee (bitter), the five basic tastants.

For quantitative assessment of flavor, we used 16 recipes familiar for Egyptians.
at presentation (baseline)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Globas Rating for smell (GRS)
Time Frame: 8 weeks, 12 weeks, 16 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
8 weeks, 12 weeks, 16 weeks, 18 weeks and 24 weeks
The Globas Rating for taste (GRT)
Time Frame: 8 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
8 weeks, 12 weeks, 18 weeks and 24 weeks
objective testings: sniffen's odor, taste and flavor identification testing
Time Frame: at 8, 12, 16, 18 and 24 weeks after intial evaluation at baseline

For quantitative assessment of smell, we used 16 odors familiar to Egyptians For quantitative assessment of taste loss, we used sugar (sweet), salt (salty), lemon (sour), old rumi cheese chips (umami) and coffee (bitter), the five basic tastants.

For quantitative assessment of flavor, we used 16 recipes familiar for Egyptians.
at 8, 12, 16, 18 and 24 weeks after intial evaluation at baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2020

Primary Completion (Actual)

September 30, 2021

Study Completion (Actual)

October 30, 2022

Study Registration Dates

First Submitted

December 24, 2020

First Submitted That Met QC Criteria

April 1, 2021

First Posted (Actual)

April 5, 2021

Study Record Updates

Last Update Posted (Estimate)

January 2, 2023

Last Update Submitted That Met QC Criteria

December 29, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COVID-NGF/AUH_SAH/2020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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