Gut feeling: probiotics with sertraline in primary care depression
| ISRCTN | ISRCTN78782742 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN78782742 |
| IRAS number | 362598 |
- Submission date
- 29/04/2025
- Registration date
- 26/06/2025
- Last edited
- 22/08/2025
- 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 mental health condition affecting millions of people worldwide. Despite existing treatments, many people continue to experience symptoms that reduce their quality of life. Research suggests that the balance of bacteria in the gut may influence mood, and that probiotics (beneficial bacteria that support gut health) might help improve mental well-being. This pilot study will explore whether it is practical and acceptable for people with moderate depression to take a probiotic alongside the antidepressant sertraline. We will also look for early signs that this combination may affect quality of life, depressive symptoms, and gastrointestinal health compared with sertraline plus a placebo (a dummy treatment 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 the 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. Preliminary changes in quality of life will be assessed using two validated questionnaires: WHOQOL-BREF and the QLDS at baseline week 2 and at endpoint week 14. Blood markers related to inflammation (hs C-reactive protein) and metabolism (lipid or fat levels) will also be examined, along with the validated mental health questionnaires, the Hamilton Depression scale, the Patient Health Questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). Depression and heart health can affect quality of life, mood, and bowel symptoms, as well as influence levels of certain blood markers.
Visit 1: Check eligibility and consent. A £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. This pilot study will test whether it is practical and acceptable to add a probiotic supplement to usual sertraline treatment for adults with depression and explore possible early improvements in quality of life and related health measures. The results will help design a larger, definitive trial in the future.
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 September 2026
Who is funding the study?
Symprove (UK)
Who is the main contact?
Dr ACMC Young, micaelayoung@nhs.net
Contact information
Principal Investigator
Orchard Court Surgery
Orchard Road
Darlington
Durham
DL3 6HX
United Kingdom
 ORCID ID |
0000-0003-1991-9589 |
|---|---|
| Phone | +44 (0)1325 465285 |
| 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 | Other |
| Participant information sheet | ISRCTN78782742_PIS_V1.3.pdf |
| Scientific title | Pilot proof-of-concept study of probiotics adjunctive to sertraline in primary care depression, exploring quality of life outcomes |
| Study acronym | PROSPECT |
| Study objectives | Current study objectives as of 20/08/2025: This proof-of-concept pilot study hypothesises that adjunctive probiotic supplementation alongside sertraline is feasible and acceptable in primary care and may provide preliminary signals of benefit for quality of life, biological markers, and depressive and gut symptoms compared with sertraline alone. Previous 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 | Current primary outcome measure as of 20/08/2025: Quality of life examined over 12 weeks using validated questionnaires World Health Organization Quality-of-Life Scale (WHOQOL-BREF) and the Quality of Life in Depression Scale (QLDS) at baseline week 2 and endpoint week 14 Previous 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 | Current secondary outcome measures as of 20/08/2025: 1. Lipid profile, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides measured with the point-of-care Cardiochek at baseline week 2 and endpoint week 14 2. High sensitivity C-reactive protein (hs-CRP) measured with point of care Eurolyser at baseline week 2 and endpoint week 14 Tertiary outcome measures: Preliminary changes in depressive and gastrointestinal symptoms assessed using the validated questionnaires Hamilton Depression Scale 17 items (HAM-D17), Patient Health Questionnaire (PHQ-9) and Gastrointestinal Symptoms Rating Scale (GSRS). at baseline (week 2) and endpoint (week 14) Feasibility outcomes: 1. Recruitment: Ability to recruit ≥20 participants per month across participating sites until the target sample of 106 participants is achieved. Timeline from initiation of study to 6 months. 2. Retention: Retention of ≥50 % of enrolled participants with dropout limited to ≤15% from baseline (week 2) to endpoint (week 14). 3. Adherence: Adherence defined as participants taking ≥80% of the allocated probiotic doses between baseline (week 2) and endpoint (week 14). 4. Acceptability and data completeness: Acceptability of study procedures assessed by the completeness of outcome data, defined as ≥80% of planned questionnaires and biological samples collected between baseline (week 2) and endpoint (week 14). Previous 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 | 01/09/2026 |
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 kg/m² 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 | 12/01/2026 |
| Date of final enrolment | 12/07/2026 |
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 | 01/09/2027 |
|---|---|
| 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 | version 1.3 | 22/08/2025 | No | Yes |
Additional files
Editorial Notes
22/08/2025: Participant information sheet uploaded.
21/08/2025: The following changes were made to the study record:
1. The study type was changed from Efficacy to Other.
2. The date of first enrolment was changed from 01/09/2025 to 12/01/2026.
3. The date of final enrolment was changed from 01/03/2026 to 12/07/2026.
4. The completion date was changed from 01/07/2026 to 01/09/2026.
5. The IRAS number was changed from 354842 to 362598.
20/08/2025: The following changes were made to the study record:
1. The public title was changed from 'Gut feeling: testing probiotics to help sertraline work better for depression' to 'Gut feeling: probiotics with sertraline in primary care depression'.
2. The scientific title was changed from 'Effect of probiotic supplementation on depression severity in primary care patients treated with sertraline: a randomized placebo-controlled trial ' to 'Pilot proof-of-concept study of probiotics adjunctive to sertraline in primary care depression, exploring quality of life outcomes'.
3. The study objectives, primary and secondary outcome measures, plain English summary and contact details were updated.
4. The intention to publish date was changed from 01/06/2027 to 01/09/2027.
07/08/2025: Internal review.
01/05/2025: Study's existence confirmed by Symprove UK.
