COVID-19 Sequelae: Treatment and Monitoring. A Dietary Supplement Based on Sea Urchin Eggs With Echinochroma A

NCT05531019 | Completed DMC

• 1 other identifier: 5832
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to assess the efficacy and efficiency of a nutraceutical from sea urchin eggs with Echinochrome A in the inflammation of tissues in subjects with long Corona Virus (COVID) syndome

Conditions

Long COVID

Keywords

Covid-19; sequalae; long covid; lung; telemedicine; brain; biomarker

Outcome Measures

Primary Outcomes (25)

• Change of symptoms over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) during rutine medical checkup.

  Measuring the symptoms as presence o absence of chest pain, cough, headache, sleep disorders, dysgeusia, myalgia, arthralgia.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change of lung capacity over four times (baseline, 4 weeks, 8 weeks, 12 weeks) assessed during spirometry.

  The main variables of forced spirometry that are measured are the forced vital capacity (FVC) and the forced expiratory volume in the first second (FEV1). The FVC represents the maximum volume of air exhaled in a maximal effort expiratory maneuver, initiated after a maximal inspiration maneuver, expressed in liters. FEV1 corresponds to the maximum volume of air exhaled in the first second of the FVC maneuver, also expressed in liters. In turn, the FEV1/FVC ratio shows the relationship between both parameters.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change of walking distance during a six minutes walk test (6MWT) over time-points (baseline, 4 weeks, 8 weeks, 12 weeks)

  The 6MWT is used, among other things, to assess and control cardiovascular and pulmonary performance below the anaerobic threshold. This test is used for the clinical evaluation of the basic motor property endurance and measures the distance a patient can walk as quickly as possible on a flat, hard surface in a period of 6 minutes. It will be measured in meters.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change of depression measured over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via the Beck Health Questionnaire.

  The Beck Anxiety Inventory is a useful tool to assess somatic symptoms of anxiety, both in anxiety disorders and depressive symptoms. The questionnaire consists of 21 questions, providing a score range between 0 and 63.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in the quality of life meassured over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via visual analog scale of EuroQol (EQ-VAS).

  EQ-VAS which is a scale of 0 to 100 that allows individuals to place themselves according to how they perceive their overall health status (0 is the worst and 100 the best health status)

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Presence or absence of Myocarditis meassured over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via electrocardiogram.

  Electrocardiographic signs in patients with myocarditis include T-wave and ST-segment abnormalities, ST-segment elevation

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in the cognitive function meassured over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via Trial Making test (TMT).

  The TMT is timed (seconds) and performed in two parts using only a pen and a piece of paper.It can provide insights into a person's cognitive function based on how fast they can search, scan, and process visual information without losing track of what they are doing.The test also provides information about a person's mental flexibility.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in the cognitive function meassured over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via Phonological verbal fluency test.

  Verbal fluency tests are commonly used to investigate lexical skills and semantic knowledge. for number of words beginning with the letters F, A, and S and for to al number of words beginning with either letter generated per minute.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in the cognitive function meassured over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via Frontal assessment battery (FAB).

  The Frontal Assessment Battery (FAB) is a cognitive test that incorporates several clinical assessments to screen for frontotemporal dementia (FTD), including S-word generation, similarities, Luria's test, grasp reflex, and the Go-No-Go test.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in the cognitive function meassured over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via clock test (CDT).

  The CDT is used to quickly assess visuospatial and praxis abilities, and may determine the presence or absence of both attention and executive dysfunctions: ask the patient to draw the face of a clock and then to draw the hands to indicate a particular time.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in the cognitive function meassured over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via Analogies (WAIS-III).

  Wais-III is an instrument for assessing Verbal Comprehension, it refers to conceptualization, knowledge and verbal expression. The subject must answer questions that measure practical knowledge, word meanings, reasoning, and the ability to express ideas in words. The Analogies subtest assesses fluid intelligence where the subject's ability to solve new problems that do not depend on schooling or formal culture is reflected: before a series of words presented, the examinee must explain the similarity of common objects or concepts that those terms represent. Maximum direct score 33 points.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in the memory over time-points ) baseline, 4 weeks, 8 weeks, 12 weeks) via Rey Auditory Verbal Learning Test.

  The test is designed as a list-learning paradigm in which the patient hears a list of 15 nouns and is asked to recall as many words from the list as possible. After five repetitions of free-recall, a second "interference" list (List B) is presented in the same manner, and the participant is asked to recall as many words from List B as possible. After the interference trial, the participant is immediately asked to recall the words from List A, which she or he heard five times previously. After a 20 min delay, the participant is asked to again recall the words from List A. After this "delayed recall" task, a list of 50 words is presented containing all of the words from Lists A. The score given for each trial is the total number of words recalled. Normal scores are 6 words hit on the first trial and 12 or 13 on the fifth trial.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in the memory over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via the memory failures of every-day (MFE)

  The Memory Failures of Everyday-MFE Questionnaire was used for the subjective assessment of memory. It consists of 28 items on situations and activities of daily living. Each item was scored on a 0-2 point scale ("never or rarely", "sometimes", "many times").

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in the overall cognitive ability over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) assessed during Addenbrooke's Cognitive Examination Revised (ACE-R) test.

  The ACE-R takes between 12 and 20 min (average 16) to administer and score in a clinical setting. It contains 5 sub-scores, each one representing one cognitive domain: attention/orientation (18 points), memory (26 points), fluency (14 points), language (26 points) and visuospatial (16 points). ACE-R maximum score is 100, composed by the addition of the all domains

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in the overall memory over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) assessed during Digit Span (WAIS-III): Forward.

  The Digit Span score is the length of the longest correctly repeated sequence. The idea was to test how much a person can receive, process and remember for a variety of elements. On average a person is not capable of retaining more than 7 pieces of information. This means that when the longest repeated sequence is 7, the participant reached level 7. The test was assessed in forward orders of the digits.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in the assess aspects such as selective attention and inhibitory control over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via Stroop test.

  Throughout the Stroop test, a total of three different tasks are carried out, through three sheets in which five columns of 20 elements appear. Each one of the tasks is carried out during a certain time (for example, forty-five seconds), scoring the successes for later evaluation. The successes that the subject has had during the test or the time it takes to react to the stimulation are valued, paying attention to what is reflected in each of the sheets or tasks.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Changes in the expression of language over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via Boston Nomination Test.

  The Boston vocabulary test consists of 60 figures, ordered from the easiest to the most difficult. The figures are presented in order, allowing the subject 20 seconds to respond. The scores provided by the test are: - The number of correct answers given spontaneously.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Changes in the expression of language over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via semantic Verbal Fluency test.

  The Semantic Verbal Fluency (SVF) test entails the generation of words from a given category within a pre-set time of 60 seconds.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Changes in sleep behaviors over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via The Pittsburgh Sleep Quality Index (PSQI)

  The Pittsburgh Sleep Quality Index (PSQI) is the most widely used sleep questionnaire in adults, consisting of 24 questions. The first 19 questions are answered by the evaluated person taking into account what they have experienced during the last month. Resultados de traducción Sleep quality index (PSQI)

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Changes in concussion over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via king figure method.

  Demonstration and test cards for the King-Devick test, a candidate rapid sideline screening for concussion based on speed of rapid number naming. To perform the King-Devick test, participants are asked to read the numbers on each card from left to right as quickly as possible, but without making any errors. Following completion of the demonstration card (upper left), subjects are then asked to read each of the three test cards in the same manner. The times required to complete each card are recorded in seconds using a stopwatch. The sum of the three test card time scores constitutes the summary score for the entire test, the King-Devick time score. Numbers of errors made in reading the test cards are also recorded; misspeaks on numbers are recorded as errors only if the subject does not immediately correct the mistake before going on to the next number.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Changes in olfactory-specific quality of life over time-points (baseline, 4 weeñs, 8 weeks, 12 weeks) via questionnaire of olfactory disorders-negative statements (QOD-NS) and a short version of QOD-NS (sQOD-NS).

  The QOD-NS questionnaire consists of 17 negative statements about the degree to which patients suffered from olfactory impairment. Patients can agree, partly agree, partly disagree, or disagree in each statement which ranges from 0 to 3. A total score of 0-51 is calculated with higher scores reflecting worse olfactory-specific quality of life. For the sQOD-NS questionnaire composed of 7 items, the total scores range from 0 to 21.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Changes in dyspnea scale over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via modified Medical Research Council (mMRC) dyspnoea scale.

  The mMRC scale is a self-rating tool to measure the degree of disability that breathlessness poses on day-to-day activities on a scale from 0 to 4: 0, no breathlessness except on strenuous exercise; 1, shortness of breath when hurrying on the level or walking up a slight hill; 2, walks slower than people of same age on the level because of breathlessness or has to stop to catch breath when walking at their own pace on the level; 3, stops for breath after walking ∼100 m or after few minutes on the level; and 4, too breathless to leave the house, or breathless when dressing or undressing.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in scale of Asthenia over time-point (baseline, 4 weeks, 8 weeks, 12 weeks) via asthenia scale.

  Analog scale from 0 to 100 mm

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in Fatigue scale over time-point (baseline, 4 weeks, 8 weeks, 12 weeks) via Krupp Clader CFQ-11 Fatigue Intensity Scale.

  The Chalder Fatigue Questionnaire (CFQ) also referred to as the Chalder Fatigue Scale, is an 11-item questionnaire measuring the severity of physical and mental fatigue on two separate subscales. Seven items represent physical fatigue (items 1-7) and 4 represent mental fatigue (items 8-11). Each item is scored 0-3; less than usual (0), no more than usual (1), more than usual (2) and much more than usual (3). The ratings of items are added together to calculate the total score (range=0-33). High scores represent high levels of fatigue.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change in Emotions scale over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via Brackets RULER scale.

  Brackets' RULER syllabus consists of five key skills, which anyone can learn. The acronym "RULER" stands for Recognize, Understand, Label, Express, and Regulate. The first three skills allow us to practice identifying our emotions. The last two allow us to develop the necessary skills to deal with them. The RULER curriculum is about gathering information by recognizing and understanding emotions. Apply emotional intelligence to various situations.

  Baseline, 4 weeks, 8 weeks, 12 weeks

Secondary Outcomes (4)

• Change of Von Willebrand Factor over time-points (baseline, 4 weeks, 12 weeks, 12 weeks) via blood sample.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change of D Dimer over time-points (baseline, 4 weeks, 12 weeks, 12 weeks) via blood sample.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change of HS-CRP over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via blood sample.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change of Ferritin over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via blood sample.

  Baseline, 4 weeks, 8 weeks, 12 weeks

Other Outcomes (3)

• Change of the emotional state over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via Plutchik's Wheel of Emotions.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change of the emotional state over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via Scale Revised by Event Impacts.

  Baseline, 4 weeks, 8 weeks, 12 weeks

• Change of the emotional state over time-points (baseline, 4 weeks, 8 weeks, 12 weeks) via Mood Person Centered Approach.

  Baseline, 4 weeks, 8 weeks, 12 weeks

Study Arms (2)

Dietary Supplement with sea urchin egg extract

EXPERIMENTAL

Ingestion of dietary supplement with 0,025% of Echinochrome A (ingested 3ml twice a day for 90 days), 1,5mg daily consumption from sea urchin egg extract (Arbacia dufresnii)

Dietary Supplement: Echinochrome A

Control

PLACEBO COMPARATOR

Ingestion of 3ml twice a day for 90 days of placebo

Other: Control

Interventions

Echinochrome A DIETARY_SUPPLEMENT

Dietary Supplement with Echinochroma A Simple randomized design, in this arm patients will take 6ml of a 0.025% Echinochroma A solution twice a day for 90 days. 3 mg of Echinochroma A will be consumed per day.

Also known as: EchA Marine

Dietary Supplement with sea urchin egg extract

Control OTHER

Simple randomized design, in this arm patients will take 6ml of an fructose aqueous solution twice a day for 90 days with the same flavor as the treatment

Control

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Positive diagnosis of COVID-19 in at least the last 12 weeks
• Diagnosis of COVID Persistent, COVID sequalea, Long COVID
• Adult men or non-pregnant adult women between the ages of 18 and 60.
• The patient (or legally authorized representative) provides your informed consent before initiating any study procedure.
• The patient (or legally authorized representative) understands and agrees comply with the planned study procedures. 6. Agreement not to participate in another trial ofintervention for the treatment of COVID-19 until day 60 after the start of the trial.

You may not qualify if:

• \. Patients without persistent COVID symptoms. 2. Patients unable to give informed consent. 3. Patients without a positive result for COVID-19. 4. Pregnancy or lactation. 5. In the doctor's opinion, the patient with advanced organ dysfunction that would not make participation appropriate.

Sponsors & Collaborators

• Fernando Saldarini: lead
• Universidad Nacional de la Patagonia San Juan Bosco: collaborator
• Ministerio de Ciencia, Tecnologia e Innovación, Argentina: collaborator
• Hospital de Infecciosas Francisco Javier Muniz: collaborator

Study Sites (1)

Hospital Donación Francisco Santojanni

Buenos Aires, 1408, Argentina

Location

Related Publications (21)

• Gorna R, MacDermott N, Rayner C, O'Hara M, Evans S, Agyen L, Nutland W, Rogers N, Hastie C. Long COVID guidelines need to reflect lived experience. Lancet. 2021 Feb 6;397(10273):455-457. doi: 10.1016/S0140-6736(20)32705-7. Epub 2020 Dec 23. No abstract available.

  PMID: 33357467 BACKGROUND

• Marshall M. The four most urgent questions about long COVID. Nature. 2021 Jun;594(7862):168-170. doi: 10.1038/d41586-021-01511-z. No abstract available.

  PMID: 34108700 BACKGROUND

• COVID-19 rapid guideline: managing the long-term effects of COVID-19. London: National Institute for Health and Care Excellence (NICE); 2024 Jan 25. Available from http://www.ncbi.nlm.nih.gov/books/NBK567261/

  PMID: 33555768 BACKGROUND

• S.E. de M.G. y de F. (SEMG), Guía clínica para la atención al paciente long COVID/COVID persistente, (2021) 1-12

  BACKGROUND

• Raveendran AV, Jayadevan R, Sashidharan S. Long COVID: An overview. Diabetes Metab Syndr. 2021 May-Jun;15(3):869-875. doi: 10.1016/j.dsx.2021.04.007. Epub 2021 Apr 20.

  PMID: 33892403 BACKGROUND

• Barker-Davies RM, O'Sullivan O, Senaratne KPP, Baker P, Cranley M, Dharm-Datta S, Ellis H, Goodall D, Gough M, Lewis S, Norman J, Papadopoulou T, Roscoe D, Sherwood D, Turner P, Walker T, Mistlin A, Phillip R, Nicol AM, Bennett AN, Bahadur S. The Stanford Hall consensus statement for post-COVID-19 rehabilitation. Br J Sports Med. 2020 Aug;54(16):949-959. doi: 10.1136/bjsports-2020-102596. Epub 2020 May 31.

  PMID: 32475821 BACKGROUND

• D. Barron, Bringing the Clinical Trial to the Patient, Eye Pharma. (2017)

  BACKGROUND

• Rubilar T, Barbieri ES, Gazquez A, Avaro M. Sea Urchin Pigments: Echinochrome A and Its Potential Implication in the Cytokine Storm Syndrome. Mar Drugs. 2021 May 11;19(5):267. doi: 10.3390/md19050267.

  PMID: 34064550 BACKGROUND

• Artyukov AA, Zelepuga EA, Bogdanovich LN, Lupach NM, Novikov VL, Rutckova TA, Kozlovskaya EP. Marine Polyhydroxynaphthoquinone, Echinochrome A: Prevention of Atherosclerotic Inflammation and Probable Molecular Targets. J Clin Med. 2020 May 15;9(5):1494. doi: 10.3390/jcm9051494.

  PMID: 32429179 BACKGROUND

• Nabavi N. Long covid: How to define it and how to manage it. BMJ. 2020 Sep 7;370:m3489. doi: 10.1136/bmj.m3489. No abstract available.

  PMID: 32895219 BACKGROUND

• Mahase E. Long covid could be four different syndromes, review suggests. BMJ. 2020 Oct 14;371:m3981. doi: 10.1136/bmj.m3981. No abstract available.

  PMID: 33055076 BACKGROUND

• Altmann DM, Boyton RJ. Decoding the unknowns in long covid. BMJ. 2021 Feb 4;372:n132. doi: 10.1136/bmj.n132. No abstract available.

  PMID: 33541867 BACKGROUND

• Del Rio C, Collins LF, Malani P. Long-term Health Consequences of COVID-19. JAMA. 2020 Nov 3;324(17):1723-1724. doi: 10.1001/jama.2020.19719. No abstract available.

  PMID: 33031513 BACKGROUND

• P. Brito-Zerón, L. Conangla Ferrín, B. Kostov, A. Moragas Moreno, M. Ramos-Casals, E. Sequeira Aymar, A. Sisó Almirall, Manfestaciones persistentes de la COVID-19 . Guía de práctica clínica, 2020.

  BACKGROUND

• A.A. Artyukov, A.M. Popov, A. V. Tsybulsky, O.N. Krivoshapko, N. V. Polyakova, Pharmacological activity of echinochrome a alone and in the biologically active additive Timarin, Biochem. Suppl. Ser. B Biomed. Chem. (2013). https://doi.org/10.1134/S1990750813030025.

  BACKGROUND

• N. Vinod, Living with 'Long COVID-19': The long-term complications and sequelae, Int. J. Clin. Virol. 5 (2021) 011-021. https://doi.org/10.29328/journal.ijcv.1001030.

  BACKGROUND

• A.N. Shikov, O.N. Pozharitskaya, A.S. Krishtopina, V.G. Makarov, Naphthoquinone pigments from sea urchins: chemistry and pharmacology, Phytochem. Rev. (2018). https://doi.org/10.1007/s11101-018-9547-3

  BACKGROUND

• C.S. Yoon, H.K. Kim, N.P. Mishchenko, E.A. Vasileva, S.A. Fedoreyev, O.P. Shestak, N.N. Balaneva, V.L. Novikov, V.A. Stonik, J. Han, The protective effects of echinochrome A structural analogs against oxidative stress and doxorubicin in AC16 cardiomyocytes, Mol. Cell. Toxicol. (2019). https://doi.org/10.1007/s13273-019-0044-6

  BACKGROUND

• I.A. González, Experiencia del paciente afectado por COVID-19 persistente acerca de la utilidad y características de las escalas de valoración clínica de los síntomas derivados de su enfermedad, Med. Gen. y Fam. 9 (2020) 121-125. https://doi.org/0.24038/mgyf.2021.018.

  BACKGROUND

• C.R. Rogers, Client-centered/person-centered approach to therapy, Vopr. Psikhol. (2001).

  BACKGROUND

• M. Méndez, Carl Rogers y Martin Buber: las actitudes del terapeuta Centrado en la Persona y la relación " Yo-Tú " en psicoterapia, Apunt. Psicol. 32 (2014) 171-180.

  BACKGROUND

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; COVID-19

Interventions

echinochrome A

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; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Tamara Rubilar, PhD

  Universidad Nacional de la Patagonia San Juan Bosco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The vials of the nutraceutical are identical to each other as well as the labels. It is impossible to distinguish one from the other.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Neumology

Model Details: Ramdomized Control

Study Record Dates

• First Submitted: August 19, 2022
• First Posted: September 7, 2022
• Study Start: September 22, 2021
• Primary Completion: December 8, 2022
• Study Completion: December 18, 2022
• Last Updated: February 28, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The data will be available six month after publication for six month
• Access Criteria: An email to the Principal Investigator

Locations

AR (1)