Clinical trial NCT06054438: Examining the Function of Cs4 on Post-COVID-19 Disorders
Official title: Examining the Immunomodulatory and Health Improving Function of a Chinese Medicine Nutritional Supplement Cs4 on Immunity-related Disorders in the Post-COVID Era
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Long COVID
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2023-09-26
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Cordyceps is a medicinal Chinese medicine. The benefits of cordyceps-related therapeutic action have been studied due to its anti-inflammation and immunomodulation features. Thus, Cordyceps may have efficacy against health problems in the post-COVID era. the Cs4 is a Chinese medicine nutritional supplement fermented by Cordyceps. This Project conducts a two-stage waitlist-controlled trial to examine the therapeutic effect of the Cs4 on long-COVID patients. 110 Patients will be recruited and divided into two groups. Each group contains 55 patients. In the first-stage clinical trial for 12 weeks, group A will have treatment while group B will have no Cs4 treatment. In the second-stage clinical trial for 12 weeks, group A will have no Cs4 treatment while group B will have Cs4 treatment. A 12-week follow-up will be conducted after the intervention of Cs4 for group A. The primary outcome will be the change from 0 to 12 weeks in symptom severity measured by self-declared modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm). In our study, we intend to analyse the efficacy of Cs4 on the improvement of long Covid symptoms by using a comprehensive measurement to cover most symptoms, and be condition-specific. The secondary outcomes will include the change from 0 to 12 weeks of Insomnia Severity Index (ISI), Brief Fatigue Inventory Form, St. George's Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS), and the Short Form 12 (SF12). Blood tests will be assessed for safety study. primary outcomes and secondary outcomes will be assessed at baseline (week 0) and week 12. The anticipated outcome of the study is to provide evidence of Cs4 in the improvement of long COVID symptoms. This project can serve to the development of a nutritional supplement for the management of post-COVID-related health problems.

Detailed description: Research Methodologies Participants Setting This is a waitlist-controlled trial to examine the therapeutic effect of Cs4 on long-COVID patients, which are divided into two groups. The study will be conducted in the Specialist Clinical Centre for Teaching and Research (Sassoon Road), School of Chinese Medicine, The University of Hong Kong (HKU).

Inclusion Criteria

1. Male or female patients with age from 18 to 75 years old, who have been previously diagnosed with COVID-19 and recovered;
2. The self-declared post-COVID-19 Functional Status scale should be at least over 1;
3. The post-COVID symptoms have lasted at least 28 days after diagnosis;
4. Currently not taking any other orally administered Chinese medicine;
5. Negative COVID-19 antigen or nucleic acid test within 3 days prior to signing the consent form;
6. Voluntary participation in this clinical study. Exclusion Criteria

1. Inability to read and/or write Chinese or English; 2. Inability to communicate (e.g. with cognitive impairment) 3. Allergy to Cordyceps sinensis; 4. Pregnant or lactating women; 5. Impaired hepatic or renal function. Methods Participants will be recruited through the webpage of the School of Chinese Medicine, HKU. Clinical history and comprehensive examination will be performed during the first interview by registered Chinese Medicine practitioners or registered nurses who will be informed about the aims, procedure and nature of the study, and possible side effects of Cs4 and written consent will be obtained from each subject who agrees to get into the study. The participant will be also informed that they have the freedom to withdraw at any time during the study.

Study design This will be a waitlist-controlled trial in which participants will alternately receive the intervention of Cs4 for 12 weeks, followed by a 12-week follow-up. 110 long-COVID patients will be randomly divided into two groups (Group A and Group B). Randomisation will be carried out according to the computer- based Excel random number generator. An integer number between 1 and 110 will be assigned to each individual at random. Group A consists of individuals assigned integer numbers between 1 and 55. Group B consists of individuals assigned integer numbers between 56 and 110.

Intervention Cs4 will be provided by Chinese Pharm, produced by GMP standard manufacturing. The intervention will be given according to the product instruction. Each capsule is 0.4g. According to the product sheet, adults should take 3-4 capsules daily as a way to nourish and strengthen the lungs and kidneys. In our study, the participants are people with long-COVID symptoms. Therefore, in order to achieve maximum efficacy, we will follow the directions and let participants take the maximum amount allowed by the product which is 4 capsules daily. Participants will take one capsule (each 400mg) 4 times a day, for a total of 1.6g. Treatment will last 12 weeks.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients with age from 18 to 75 years old, who have been previously diagnosed with COVID-19 and recovered;
2. The self-declared post-COVID-19 Functional Status scale should be at least over 1;
3. The post-COVID symptoms have lasted at least 28 days after diagnosis;
4. Currently not taking any other orally administered Chinese medicine;
5. Negative COVID-19 antigen or nucleic acid test within 3 days prior to signing the consent form;
6. Voluntary participation in this clinical study.

Exclusion Criteria:

1. Inability to read and/or write Chinese or English;
2. Inability to communicate (e.g. with cognitive impairment) 3. Allergy to Cordyceps sinensis;

4. Pregnant or lactating women; 5. Impaired hepatic or renal function.

Primary outcomes:
measure: the change in symptom severity from 0 to 12 weeks measured by the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm)
timeFrame: will be assessed at baseline and 12 weeks.
Secondary outcomes:
measure: the change in Insomnia Severity Index (ISI) from 0 to 12 weeks
timeFrame: will be assessed at baseline and 12 weeks.
measure: the change in Brief Fatigue Inventory Form (BFI) from 0 to 12 weeks
timeFrame: will be assessed at baseline and 12 weeks.
measure: the change in St. George's Respiratory Questionnaire (SGRQ) from 0 to 12 weeks
timeFrame: will be assessed at baseline and 12 weeks.
measure: the change in Hospital Anxiety and Depression Scale (HADS) from 0 to 12 weeks
timeFrame: will be assessed at baseline and 12 weeks.
measure: the change in Short Form 12 (SF12) from 0 to 12 weeks
timeFrame: will be assessed at baseline and 12 weeks.
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: The School of Chinese Medicine, HKU
Study officials:
affiliation: The University of Hong Kong
name: Yibin Feng, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Chen J, Chan WM, Leung HY, Leong PK, Yan CTM, Ko KM. Anti-Inflammatory Effects of a Cordyceps sinensis Mycelium Culture Extract (Cs-4) on Rodent Models of Allergic Rhinitis and Asthma. Molecules. 2020 Sep 4;25(18):4051. doi: 10.3390/molecules25184051.
citation: Han F, Dou M, Wang Y, Xu C, Li Y, Ding X, Xue W, Zheng J, Tian P, Ding C. Cordycepin protects renal ischemia/reperfusion injury through regulating inflammation, apoptosis, and oxidative stress. Acta Biochim Biophys Sin (Shanghai). 2020 Feb 3;52(2):125-132. doi: 10.1093/abbs/gmz145.
citation: Klok FA, Boon GJAM, Barco S, Endres M, Geelhoed JJM, Knauss S, Rezek SA, Spruit MA, Vehreschild J, Siegerink B. The Post-COVID-19 Functional Status scale: a tool to measure functional status over time after COVID-19. Eur Respir J. 2020 Jul 2;56(1):2001494. doi: 10.1183/13993003.01494-2020. Print 2020 Jul.
citation: Sivan M, Preston N, Parkin A, Makower S, Gee J, Ross D, Tarrant R, Davison J, Halpin S, O'Connor RJ, Horton M. The modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) patient-reported outcome measure for Long Covid or Post-COVID-19 syndrome. J Med Virol. 2022 Sep;94(9):4253-4264. doi: 10.1002/jmv.27878. Epub 2022 Jun 1.