Gut feeling: testing probiotics to help sertraline work better for depression
| ISRCTN | ISRCTN78782742 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN78782742 |
| IRAS number | 354842 |
- Submission date
- 29/04/2025
- Registration date
- 26/06/2025
- Last edited
- 26/06/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Mental and Behavioural Disorders
Plain English summary of protocol
Background and study aims
Depression is a common condition that affects millions of people worldwide. Research suggests that the balance of bacteria in the gut may influence mental health. Probiotics, which are beneficial bacteria, have shown potential in improving gut health and possibly supporting mental well-being. However, their effectiveness in treating depression, especially when used alongside antidepressants like sertraline, remains unclear.
This study aims to explore whether taking probiotics alongside sertraline leads to better outcomes for people with moderate depression, compared to taking sertraline with a placebo (a substance with no active ingredients).
Who can participate?
People aged 18 to 60 years with moderate depression
What does the study involve?
Participants will be randomly assigned to receive either sertraline with the probiotic liquid drink, Symprove (containing predominantly Lactobacillus strains), or sertraline with a placebo, identical in appearance but lacking active ingredients, for 12 weeks. Neither the participants nor researchers know who is receiving the real treatment (probiotics) and who is receiving the placebo (a dummy treatment with no active ingredients). This makes the study as fair and reasonable as possible.
Informed consent will be obtained through face-to-face discussions, highlighting potential side effects and ensuring the right to withdraw at any time without compromising clinical care. The participant’s GP will be informed of their involvement in the study, in case it affects their care. Confidentiality will be maintained through anonymisation, with physical documentation stored securely and digital data encrypted.
The overall burden of participation will be 5 visits over 14 weeks. Changes in depression symptoms will be assessed using two widely used mental health questionnaires, the Hamilton Depression scale and the Patient Health Questionnaire. Blood markers related to inflammation (hs C-reactive protein) and metabolism (lipid or fat levels) will also be examined, along with the validated gastrointestinal symptom rating scale (GSRS) to monitor bowel symptoms. Depression and heart health can have an influence on the level of these markers and bowel symptoms.
Visit 1: Check eligibility and consent. £20 participation voucher will be offered at completion.
Visit 2: Randomisation, confirm consent, answer questionnaires with a psychologist and have bloods, BP and BMI taken. Participants will be issued a code to collect the liquid drink.
Visit 3: See health care to assess progress, concordance with liquid drink, discuss any adverse effects, review consent with freedom to withdraw. Access to medical advice if needed. Further code for liquid drink.
Visit 4: Same as visit 3.
Visit 5: As visit 3 but without the code for the liquid drink. There will be repeat questionnaires with a psychologist, bloods, BMI and issue of voucher. Participants will be informed of the results of the study 3 months after completion, in a manner of their choosing, either by post, email or accessing the practice website.
What are the possible benefits and risks of participating?
Participants will benefit from regular check-ups on their mental and physical health throughout the study. Some may experience mild side effects from the probiotic, such as bloating or more frequent bowel movements, but previous research has found these to be minor. While we cannot guarantee that taking part will improve mood or heart health, there is a possibility of these benefits.
The main purpose of the study is to help advance research, which could lead to better treatment options in the future. It may provide the first clinically meaningful evaluation of probiotics as an addition to sertraline in the treatment of moderate depression in real-life primary care, offering valuable insights for future research and clinical practice.
Where is the study run from?
Denmark Street Surgery (UK)
When is the study starting and how long is it expected to run for?
December 2024 to July 2026
Who is funding the study?
Symprove (UK)
Who is the main contact?
Dr ACMC Young, micaelayoung@nhs.net
Contact information
Principal Investigator
Diabetes and Endocrinology Department
Darlington Memorial Hospital
Hollyhurst Road
Darlington
Durham
DL3 6HX
United Kingdom
 ORCID ID |
0000-0003-1991-9589 |
|---|---|
| Phone | +44 (0)1325 380100 |
| ahmetfuat@nhs.net |
Scientific
Denmark Street Surgery
Darlington
Durham
DL3 0PD
United Kingdom
| Phone | +44 (0)1325 460731 |
|---|---|
| micaelayoung@nhs.net |
Public
Denmark Street Surgery
Darlington
Durham
DL3 0PD
United Kingdom
| Phone | +44 (0)1325 460731 |
|---|---|
| paul.conroy1@nhs.net |
Study information
| Study design | Single-centre interventional double-blinded randomized controlled trial pilot |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | GP practice |
| Study type | Efficacy |
| Participant information sheet | 47251_PIS.pdf |
| Scientific title | Effect of probiotic supplementation on depression severity in primary care patients treated with sertraline: a randomized placebo-controlled trial |
| Study acronym | PROSPECT |
| Study objectives | The proposed study will investigate the effectiveness of an add-on probiotic with sertraline in moderate to major depression in primary care. The hypothesis is that the combination of probiotic and sertraline will reduce validated depression questionnaire scores as the primary outcome and reduce inflammatory and metabolic markers as secondary outcomes. |
| Ethics approval(s) |
Not yet submitted (Address not provided, City not provided, Zip/postal code not provided, United Kingdom; Telephone number not provided; a@a), ref: Reference number not provided |
| Health condition(s) or problem(s) studied | Depression |
| Intervention | The pilot will be conducted over 14 weeks. 106 participants will be randomly allocated, using a computer generator (Sealed Envelope) to ensure double-blindedness, into two groups. Group 1 will be composed of participants diagnosed with depression and prescribed sertraline with Symprove probiotic supplement. Group 2 will be composed of participants diagnosed with depression prescribed sertraline with a placebo. The daily 70 ml dose of the investigational liquid product will initially be administered by the practice health researcher, to be continued by the participant. |
| Intervention type | Supplement |
| Primary outcome measure | Depression symptoms will be assessed using the Hamilton Depression Scale (HAM-D17) and Patient Health Questionnaire (PHQ-9) at the commencement and conclusion of the pilot at week 1 and week 14 |
| Secondary outcome measures | 1. Lipid profile, cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides measured with point of care Cardiochek at week 2 and week 14 2. High sensitivity C-reactive protein (hs-CRP) measured with point of care Eurolyser at week 2 and week 14 |
| Overall study start date | 01/12/2024 |
| Completion date | 01/07/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 60 Years |
| Sex | Both |
| Target number of participants | 106 |
| Key inclusion criteria | 1. Depressive disorder diagnosed by the International Classification of Diseases (ICD)-11 2. Age 18 to 60 years 3. HAM-D17 score of 17 and PHQ-9 score of 10 4. Therapeutic antidepressant dose unchanged in the prior 3 weeks |
| Key exclusion criteria | 1. Pregnancy 2. An infection/vaccination and/or antibiotics 3. Supplementation with pro- or prebiotics 4. Autoimmune disease, inflammatory bowel disease, coeliac disease 5. BMI >35 6. Cancer, 7. Atherosclerotic cardiovascular disease (ASCVD), ischaemic heart disease (IHD), transient ischaemic attack (TIA ), peripheral arterial disease (PAD) 8. Kidney failure with estimated glomerular filtration rate (eGFR) <30 ml/min1.72m2 9. Unstable thyroid function (thyroid stimulating hormone [TSH] <0.27 or >4.2 µIU/ml) 10. Psychiatric comorbidities of psychosis, emotionally unstable personality disorder (EUPD), eating disorder, obsessive compulsive disorder (OCD) and neurodevelopmental disorders 11. Formal psychological interventions 12. Concomitant medication of benzodiazepines, z drugs and quetiapine 13. Regular treatment (more than 3 days a week) with proton pump inhibitors, metformin, laxatives, systemic steroids, or non-steroidal anti-inflammatories 14. Significant change in dietary, smoking pattern or daily physical activity in the previous 4 weeks 15. High suicide risk, assessed by Columbia Suicide Severity Rating Scale (C-SSRS) 16. Substance or alcohol misuse 17. Participation in, or recently participated in, another study involving interventions which might affect the study outcomes 18. Any other condition which would affect the compliance or safety of the individual |
| Date of first enrolment | 01/09/2025 |
| Date of final enrolment | 01/03/2026 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Darlington
DL3 0PD
United Kingdom
Sponsor information
Industry
Sandy Farm
The Sands
Farnham
GU10 1PX
England
United Kingdom
| Phone | +44 (0)125 2413600 |
|---|---|
| sammie@symprove.com | |
| Website | https://symprove.com |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 01/06/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a peer review journal |
| IPD sharing plan | The data set generated during and /or analysed during the current study will be available on request from Dr ACMC Young (micaelayoung@nhs.net). Anonymised data will be made available, with participant consent at the conclusion of the study for 6 months on request from validated researchers for clinical analyses. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 01/05/2025 | No | Yes |
Additional files
Editorial Notes
01/05/2025: Study's existence confirmed by Symprove UK.
