Trial of the functional food Biobran in patients with persistent symptoms attributed to Lyme borreliosis
| ISRCTN | ISRCTN31318565 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN31318565 |
| Secondary identifying numbers | V2 |
- Submission date
- 25/06/2017
- Registration date
- 28/06/2017
- Last edited
- 09/09/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Lyme disease is a bacterial infection spread to humans by infected ticks. This study focuses on boosting the immune system of Lyme disease patients using a food supplement called Biobran - a water-soluble rice bran extract. The aim of this study is to investigate whether daily supplementation with Biobran over three months improves immune system functioning in patients with persistent symptoms due to Lyme disease.
Who can participate?
Patients aged 18 or over with Lyme disease
What does the study involve?
Patients undergo an assessment which includes a clinical history, questionnaires, a physical examination and a blood test. This takes a morning or afternoon. The patients are randomly allocated to be given either Biobran or a placebo (dummy supplement) to take daily for three months. At the end of three months, another assessment takes place, which will be similar to the first one.
What are the possible benefits and risks of participating?
Possible benefits include undergoing an assessment, including history, which might indicate the presence of a previously unknown or unsuspected clinically relevant finding. There are no anticipated possible risks.
Where is the study run from?
The TBD Clinic (UK)
When is the study starting and how long is it expected to run for?
August 2016 to December 2023
Who is funding the study?
Daiwa (Japan)
Who is the main contact?
Prof. B Puri, bpuri@cantab.net
Contact information
Scientific
The TBD Clinic
233 New Church Road
Hove
BN3 4EE
United Kingdom
 ORCID ID |
0000-0001-6101-0139 |
|---|---|
| bpuri@cantab.net |
Study information
| Study design | Single-centre randomized double-blind placebo-controlled three-month trial (the baseline data [patients versus controls] will constitute an initial cross-sectional cohort study) |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Randomised, double-blind, placebo-controlled three-month trial of Biobran MGN-3 in patients with persistent symptoms attributed to Lyme borreliosis |
| Study objectives | There is good evidence that the functional food Biobran MGN-3 is a safe immunomodulator which enhances NK cell activity, enhances human T lymphocyte and human B lymphocyte proliferation, enhances phagocytosis of bacteria, enhances the oxidative burst in human neutrophils and monocytes, and enhances the production of the cytokines TNF-α, IL-6, IL-8 and IL-10. It is therefore hypothesised that regular daily intake of this functional food will be associated with improved immune system functioning in patients with persistent symptoms attributed to Lyme borreliosis. |
| Ethics approval(s) | AONMREC (The Academy of Nutritional Medicine Research Ethics Committee), 22/02/2017, ref: 0217 |
| Health condition(s) or problem(s) studied | Persistent symptoms attributed to Lyme borreliosis |
| Intervention | Current interventions as of 18/08/2022: Following baseline assessment, each patient will be randomly allocated to either the active group or the placebo group, in a one-to-one allocation ratio. This randomisation will be computerised and balanced by minimisation for age, sex and duration of symptoms. The researchers directly involved in the study and the participants will be blinded to group allocation. 1. Active: Biobran MGN-3 at a dose of 3 grams daily for three months. Administration: oral 2. Placebo: of identical appearance and taste to the active intervention, and isocaloric with the active intervention. Administration: oral Measurements will be made at two time-points, namely at baseline and at three-month follow-up _____ Previous interventions: Following the baseline assessment of the patients and controls, each patient will be randomly allocated to either the active group or the placebo group, in a one-to-one allocation ratio. This randomisation will be computerised and balanced by minimisation for age, sex and duration of symptoms. The researchers directly involved in the study and the participants will be blinded to group allocation. 1. Active: Biobran MGN-3 at a dose of 3 grams daily for three months. Administration: oral 2. Placebo: of identical appearance and taste to the active intervention, and isocaloric with the active intervention. Administration: oral Measurements will be made at two timepoints, namely at baseline and at three-month follow-up. |
| Intervention type | Supplement |
| Primary outcome measure | Current primary outcome measure as of 18/08/2022: Immune system functioning measured using RNA-seq and flow cytometry at baseline and three-month follow-up _____ Previous primary outcome measure: Immune system functioning, assessed using flow cytometry at baseline and three-month follow-up |
| Secondary outcome measures | Current secondary outcome measure as of 18/08/2022: 1. The following questionnaires will be administered at baseline and three-month follow-up: 1.1. Epworth Sleepiness Scale (Johns, 1991) 1.2. Overactive Bladder Symptom and Health-Related Quality of Life Questionnaire (OAB-q) (Coyne et al., 2002) 1.3. Refined and Abbreviated Composite Autonomic Symptom Score (COMPASS 31) (Sletten et al., 2012) 1.4. Modified Chalder Fatigue Scale (CFQ) (Chalder et al., 1993) 1.5. Fatigue Severity Scale (FSS) (Krupp et al., 1989) 1.6. Pain Visual Analogue Scale (VAS) (Portenoy and Kanner, 1996) 1.7. McGill Pain Questionnaire (MPQ) (Melzack, 1975) 1.8. Tinnitus Handicap Inventory (THI) (Newman et al., 1996) 2. Course of Lyme disease symptomatology, assessed by history taking, clinical examination and the use of questionnaires at baseline and three-month follow-up _____ Previous secondary outcome measure: 1. Electrocardiographic function, assessed using electrocardiography 2. Neuropsychological outcome, assessed using the Cambridge Neuropsychological Test Automated Battery. The questionnaires will be as follows: 2.1. Rheumatoid Arthritis Severity Scale (RASS) (Bardwell et al., 2002) 2.2. Epworth Sleepiness Scale (Johns, 1991) 2.3. Overactive Bladder Symptom and Health-Related Quality of Life Questionnaire (OAB-q) (Coyne et al., 2002) 2.4. Refined and Abbreviated Composite Autonomic Symptom Score (COMPASS 31) (Sletten et al., 2012) 2.5. Modified Chalder Fatigue Scale (CFQ) (Chalder et al., 1993) 2.6. Fatigue Severity Scale (FSS) (Krupp et al., 1989) 2.7. Pain Visual Analogue Scale (VAS) (Portenoy and Kanner, 1996) 2.8. McGill Pain Questionnaire (MPQ) (Melzack, 1975) 2.9. Tinnitus Handicap Inventory (THI) (Newman et al., 1996) 3. Course of Lyme disease symptomatology, assessed by history taking, clinical examination and the use of questionnaires Assessments made at baseline and three-month follow-up |
| Overall study start date | 29/08/2016 |
| Completion date | 31/12/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 52 patients |
| Total final enrolment | 20 |
| Key inclusion criteria | For the patients, the inclusion criteria will be as follows: 1. Meeting the diagnostic criteria for the syndrome of Borrelia-associated persistent symptoms used by the Persistent Lyme Empiric Antibiotic Study Europe (PLEASE); PLEASE criterion 2B will be extended to include other appropriate laboratory tests including the Elispot. PLEASE criterion #1 specifies that the subjects must be males or non-pregnant, non-lactating females who are 18 years of age or older For the controls, the inclusion criteria will be as follows: 1. Healthy males or non-pregnant, non-lactating females who are 18 years of age or older |
| Key exclusion criteria | Current participant exclusion criteria as of 18/08/2022: 1. A history of hypersensitivity to Biobran MGN-3 2. Having received > 5 days’ antimicrobial therapy during the previous four weeks 3. Regularly taking Biobran MGN-3 during the previous four weeks 4. Current enrolment in another clinical trial 5. Currently receiving other antimicrobial therapy 6. An inability to give full informed consent 7. Currently pregnant or breastfeeding _____ Previous participant exclusion criteria: For the patients, the exclusion criteria will be as follows. 1. A history of hypersensitivity to Biobran MGN-3 2. Having received > 5 days’ antimicrobial therapy during the previous four weeks 3. Regularly taking Biobran MGN-3 during the previous four weeks 4. Current enrolment in another clinical trial 5. Currently receiving other antimicrobial therapy 6. An inability to give full informed consent For the controls, the exclusion criteria will be as follows. 1. Suffering from Lyme disease or a major neuropsychiatric disorder 2. Being the child of a known Lyme disease affected mother 3. Being in a non-platonic relationship with a known Lyme disease patient |
| Date of first enrolment | 30/06/2017 |
| Date of final enrolment | 10/10/2023 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
United Kingdom
Sponsor information
Industry
1-16-19 Sangenjaya
Setagaya-ku
Tokyo
#154-0024
Japan
"ROR" |
https://ror.org/007pxvx88 |
|---|
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 31/03/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Current publication and dissemination plan as of 18/08/2022: The findings of the study will be communicated to colleagues and the public in lectures, academic journals and public talks. The trial results will not be available until the group allocation coding is broken, which will be at the end of the final assessment of the final patient; the corresponding results will be submitted for publication after this date. _____ Previous publication and dissemination plan: The findings of the study will be communicated to colleagues and the public in lectures, academic journals and public talks. The baseline data, from baseline assessments of the patients and controls, will be analysed first; it is intended that these results be submitted for publication from the last quarter of 2017 onwards. The overall trial results will not be available until the group allocation coding is broken, which will be at the end of the final assessment of the final patient; the corresponding results will be submitted for publication after this date. |
| IPD sharing plan | The datasets will not be made available in order fully to ensure patient confidentiality. Consent forms, questionnaires and identifying information will be kept in a locked filing cabinet and only the investigators involved in the study will have a key. All data will be rendered anonymous on entry into spreadsheets and statistical analysis software and held in password-protected hardware. Hard copies of data will be kept in locked filing cabinets and only the investigators involved in the study will have a key. |
Editorial Notes
09/09/2024: The intention to publish date was changed from 31/03/2024 to 31/03/2025.
03/10/2023: The total final enrolment was added.
04/07/2023: The recruitment end date was changed from 31/07/2023 to 10/10/2023.
10/02/2023: The following changes were made to the trial record:
1. Contact details updated.
2. The recruitment end date was changed from 30/12/2022 to 31/07/2023.
3. The overall trial end date was changed from 31/07/2023 to 31/12/2023.
4. The intention to publish date was changed from 01/09/2023 to 31/03/2024.
18/08/2022: The following changes have been made and the plain English summary has been updated accordingly:
1. The overall trial end date has been changed from 31/12/2018 to 31/07/2023.
2. The interventions have been changed.
3. The secondary outcome measures have been changed.
4. The participant type has been changed from ‘mixed’ to ‘patient’.
5. The participant exclusion criteria have been changed.
6. The recruitment end date has been changed from 28/09/2018 to 30/12/2022.
7. A trial centre has been changed.
8. The target number of participants was changed from 104 (comprising 52 patients and 52 controls) to 52 patients.
9. The total target enrolment has been changed from 104 to 52.
10. The publication and dissemination plan has been changed.
11. The intention to publish date has been changed from 01/09/2017 to 01/09/2023.
12. The primary outcome measures have been changed.
