Cognitive DeclineNeuroFitNCT05397990
The Impact of Exercise on Hippocampus-dependent Cognition and the Gut Microbiota
A study testing Exercise in people with Cognitive Decline, run by King's College London at 1 site in United Kingdom.
Trial summary
The NeuroFit study will be investigating the impact of exercise on global cognition, hippocampus-dependent memory function and the gut microbiota in a middle-aged population. Read more about this study
- Who is it for?
- Ages 45 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Cognitive Decline
- What is being tested?
- Exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Mar 2022to 18 Nov 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 45 - 65 years of age.
- BMI 20 - 30.
- Does less than 90 minutes of moderate to vigorous physical activity per week and does not have a regular exercise routine(captured by self-reported measures)
Who cannot join
- Subject is unable to understand the participant information sheet.
- Subject is unable to provide written informed consent.
- Subject is unable to understand and/or completely perform the cognitive testing.
- Impaired vision that is not corrected.
- Subject is a smoker.
- Does not agree to maintain their habitual dietary routine.
Show all 30Show fewer
- Unwilling to provide blood and stool samples.
- Is not in general good health on the basis of medical history.
- Unable to engage in a structured exercise program as determined by the physical activity readiness questionnaire (PARQ).
- Unwilling to engage in the prescribed exercise program 3 times a week.
- Subject is pregnant, lactating or planning pregnancy.
- Recent history (previous 2 years) or currently diagnosed with a significant psychiatric disorder including major depressive disorder, anxiety, bipolar disorder, schizophrenia or any other Diagnostic Statistical Manual (DSM)-IV Axis I disorder.
- Subject has significant acute or chronic co-existing cardiovascular, respiratory, gastrointestinal illness or liver disease.
- Subject has had major GI surgery including bariatric surgery (excluding appendectomy and cholecystectomy).
- History of cancer in the last 5 years (excluding melanoma).
- Subject has significantly out of range blood test results from screening visit.
- History of or currently diagnosed with a functional GI disorder including inflammatory bowel disease (including Crohn's disease and ulcerative colitis), coeliac disease, lactose intolerance and clinical diagnosis of irritable bowel syndrome.
- Subject has irritable bowel syndrome, functional diarrhoea or functional constipation as determined by the Rome IV.
- Subject has any neurological disorder that could produce cognitive deterioration including Alzheimer's disease, Parkinson's disease, and stroke.
- Subject has a neurodevelopmental disorder that impacts ability to take part in cognitive testing and/or memory function.
- History of traumatic brain injury, stroke or any other medical conditions causing cognitive impairment.
- Subject has uncontrolled epilepsy or is prone to fainting.
- Subject has an eating disorder.
- History of or currently diagnosed with a metabolic disorder including type 1 and type 2 diabetes mellitus.
- Subject is unwilling to stop taking prebiotics or probiotics for at least 4 weeks prior to commencing the study.
- Known or suspected of alcohol abuse defined as > 14 drinks per week (1 drink = 1 pint of beer, 1 large glass of wine or 50 ml spirit).
- Subject has a sleep disorder or an occupation where sleep during the overnight hours is irregular.
- Subjects routinely taking psychoactive medications, laxatives, enemas, antibiotics, anticoagulants, NSAIDs, proton pump inhibitors and unwilling to stop at least 4 weeks prior to commencing the study.
- Subjects taking the following prescription medications: Statins, Metformin, Donepezil (Aricept), Galantamine (Reminyl), Rivastigmine (Exelon), Tacrine (Cognex), Memantine (Namenda), Selegiline (Eldepryl) or any other medication for cognitive impairment.
- Subject has a condition the chief investigator believes would interfere with their ability to provide informed consent, comply with the study protocol, may confound the interpretation of study results, or put the subject at undue risk.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Investigating the Impact of Exercise on Hippocampus-dependent Cognition and the Gut Microbiota in a Healthy, Middle-aged Population: The NeuroFit Study
The NeuroFit study will be investigating the impact of exercise on global cognition, hippocampus-dependent memory function and the gut microbiota in a middle-aged population.
Read the detailed description
Main research question: Does exercise have an impact on global cognition, hippocampus-dependent memory function and the gut microbiota in a middle-aged human population?
Middle-age is a critical time for cognitive/mood changes and precedes prodromal dementia, which is mediated by changes in neuroplasticity and altered gut microbiota. This period of the lifespan is also associated with weight gain, decline in metabolism and physical fitness. Yet, it is unclear if cognitive and mood changes can be ameliorated in response to exercise and the role of gut microbiota.
The hippocampus plays a role in cognition and mood and is vulnerable to gut-mediated and metabolic changes. It is capable of generating new neurons from neural stem cells throughout life. This is a modifiable process of neuroplasticity called adult hippocampal neurogenesis (AHN), which decreases with age in the human and rodent brain. Exercise is a robust enhancer of AHN and attenuates deficits in the aged brain. Rodent studies have shown that AHN underlies antidepressant effects and certain forms of memory. In particular, pattern separation, the ability to discriminate between similar experiences or environments. A reduced ability to pattern separate is evident in older individuals and is an early symptom in mild cognitive impairment, which can present during middle-age. Moreover, pattern separation has been shown to be impaired and AHN decreased in middle-aged relates compared to young rats. Pattern separation has also been implicated as critically sensitive to exercise. However, the potential for exercise to prevent/reverse a deficit in AHN and pattern separation in middle-age has not yet been investigated. A major gap in knowledge is the identification of the mechanisms underlying cognitive impairment in middle-age, and how modulating factors, such as exercise, could attenuate them.
The investigators propose that the composition of the gut microbiota and their metabolites in middle-age may predict reduced AHN and pattern separation, which may be rescued/improved by exercise, and is thus a key mechanistic target for investigation. In support, ageing is associated with a decline in gastrointestinal function and a change in microbiota composition. Middle-age is particularly vulnerable for gut microbiota compositional and metabolite changes coupled with neuroinflammation in mice, and that these effects are modified in response to prebiotic supplementation. An altered gut microbiota is associated with low mood/depressive behaviour through metabolic changes, and germ-free mice display an aberrant increase of neurogenesis. Moreover, preliminary data show that gut microbiota depletion (induced by long-term antibiotic administration) leads to a decrease in pattern separation and AHN, albeit in young adult rats.
Accumulating evidence suggests that exercise can change gut microbial composition and serum metabolites. Interestingly, human and rats present the same metabolic signature in plasma after exercise. Moreover, the effects of exercise on metabolic profiles are transmissible via faecal microbiota transplantation (FMT). Considering the gut microbiota (i) is sensitive to exercise and age, (ii) regulates AHN and, (iii) is involved in pattern separation and mood, the investigators propose that the gut microbiome-AHN communication is important in maintaining hippocampal integrity and cognitive function during middle-age.
Aim The overall aim of the NeuroFit study is to develop and test the impact of a group-based exercise intervention to identify specific gut microbiota and metabolic signatures that may influence cognitive and mood changes in middle-aged adults.
Hypothesis Reduced pattern separation in middle age can be rescued/improved by exercise accompanied by changes in the gut microbiota and related metabolites.
Objectives The NeuroFit study has 3 main objectives.
- Determine the impact of a 12-week exercise intervention (30 minutes, 3 days a week) compared to a control group (continued habitual behaviour) in healthy, middle-aged participants on cognition and mood.
- Identify specific gut microbiota and metabolic signatures in middle age which is responsive to exercise and predictive of cognitive and mood changes in a randomised controlled trial.
- Assess the impact of exercise on neuropsychiatric symptoms, serum BDNF, dietary intake, quality of life, habitual physical activity, cardio-respiratory fitness, anthropometry and cardiometabolic health on cognition and mood.
- Conditions
- Cognitive Decline
- Being tested
- Exercise
- Keywords
- Cognition, Pattern separation, Memory function, Gut microbiota, Exercise, Neurogenesis, Lifestyle
- Medical subject headings
- Cognitive Dysfunction, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExerciseBehavioural
12 weeks of moderate intensity exercise, three times a week.
| Study group | Role | What they receive |
|---|---|---|
| Exercise | Experimental | 12 weeks exercise intervention. 3 times a week, 45 minutes per session, 30 minutes of exercise. Receives: Behavioral: Exercise |
| Control | No intervention | Continue with habitual routine. Take part in weekly online socials with others in the control group. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mnemonic Similarity Task
Pattern separation and recognition memory
Measured: Change from baseline pattern separation and recognition memory at 12 weeks
Mnemonic Similarity Task
Pattern separation and recognition memory
Measured: Change from baseline pattern separation and recognition memory at 24 weeks
Secondary outcomes (13)
Patient Health Questionnaire 9
Mood score Scoring scale: 0 - 27 Lower scores = better outcome.
Measured: Change from baseline mood at 12 weeks
Patient Health Questionnaire 9
Mood score Scoring scale: 0 - 27 Lower scores = better outcome.
Measured: Change from baseline mood at 24 weeks
Gut microbiome composition
Taken from participant stool samples. Measured using shotgun metagenomic sequencing.
Measured: Change from baseline composition at 12 weeks
Metabolomic profile - Serum
Metabolomic screen of participant serum samples at MS-Omics (Denmark)
Measured: Change from baseline profile at 12 weeks
Metabolomic profile - Gut microbiota
Metabolomic screen of participant stool samples at MS-Omics (Denmark)
Measured: Change from baseline profile at 12 weeks
Short Form 12
Quality of life scale Scoring scale: 0 - 100 Higher scores = better outcome.
Measured: Change from baseline quality of life at 12 weeks
Short Form 12
Quality of life scale Scoring scale: 0 - 100 Higher scores = better outcome.
Measured: Change from baseline quality of life at 24 weeks
Cardiorespiratory fitness
3 minute step test
Measured: Change from baseline fitness at 12 weeks
Cardiorespiratory fitness
3 minute step test
Measured: Change from baseline fitness at 24 weeks
Bone derived neurotrophic factor (BDNF)
Measured from participant serum sample using an enzyme-link immunoabsorbant assay
Measured: Change from baseline BDNF levels at 12 weeks
Bone derived neurotrophic factor (BDNF)
Measured from participant serum sample using an enzyme-link immunoabsorbant assay
Measured: Change from baseline BDNF levels at 24 weeks
Nutritional intake
4 day food diary
Measured: Change from baseline nutritional intake at 12 weeks
Nutritional intake
4 day food diary
Measured: Change from baseline nutritional intake at 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2022
- Study start1 Mar 2022
- Primary completion18 Nov 2024
- Study completion18 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cognitive DeclineStudies of the same condition, open and under way.
- More trials run by King's College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Collaborators
- Reta Lila Weston Trust, University College Cork
- Responsible party
- Sponsor
- Investigators
- Sandrine Thuret, PhD, Principal investigator, King's College LondonBrendon Stubbs, PhD, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05397990
- Sponsor's protocol ID
- HR/DP-21/22-28287
- Acronym
- NeuroFit
- Status last verified
- Oct 2023
- First submitted
- 20 May 2022
- Last updated
- 7 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymised study data
Publications
Farmand S, Kim C, Du Preez A, Werneck AO, Batzu L, Pearce D, Brady K, Khir M, Nicolas S, Cryan JF, Nolan YM, Stubbs B, Thuret S. Effects of a three-month exercise programme on cognition, mood and neurogenesis: the NeuroFit randomised controlled trial. NPJ Aging. 2026 Sep 17;12(1):124. doi: 10.1038/s41514-026-00439-w.
PubMed 42754613
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Impact of Exercise on Hippocampus-dependent Cognition and the Gut Microbiota in a Healthy, Middle-aged Population: The NeuroFit Study
- ClinicalTrials.gov ID
- NCT05397990
- Acronym / sponsor ID
- NeuroFit / HR/DP-21/22-28287
- Conditions
- Cognitive Decline
- Keywords
- Cognition, Pattern separation, Memory function, Gut microbiota, Exercise, Neurogenesis, Lifestyle
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- Reta Lila Weston Trust, University College Cork
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 18 Nov 2024 (actual)
- Study completion
- 18 Nov 2024 (actual)
- First posted
- 31 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The NeuroFit study will be investigating the impact of exercise on global cognition, hippocampus-dependent memory function and the gut microbiota in a middle-aged population.
Detailed description
Main research question: Does exercise have an impact on global cognition, hippocampus-dependent memory function and the gut microbiota in a middle-aged human population?
Middle-age is a critical time for cognitive/mood changes and precedes prodromal dementia, which is mediated by changes in neuroplasticity and altered gut microbiota. This period of the lifespan is also associated with weight gain, decline in metabolism and physical fitness. Yet, it is unclear if cognitive and mood changes can be ameliorated in response to exercise and the role of gut microbiota.
The hippocampus plays a role in cognition and mood and is vulnerable to gut-mediated and metabolic changes. It is capable of generating new neurons from neural stem cells throughout life. This is a modifiable process of neuroplasticity called adult hippocampal neurogenesis (AHN), which decreases with age in the human and rodent brain. Exercise is a robust enhancer of AHN and attenuates deficits in the aged brain. Rodent studies have shown that AHN underlies antidepressant effects and certain forms of memory. In particular, pattern separation, the ability to discriminate between similar experiences or environments. A reduced ability to pattern separate is evident in older individuals and is an early symptom in mild cognitive impairment, which can present during middle-age. Moreover, pattern separation has been shown to be impaired and AHN decreased in middle-aged relates compared to young rats. Pattern separation has also been implicated as critically sensitive to exercise. However, the potential for exercise to prevent/reverse a deficit in AHN and pattern separation in middle-age has not yet been investigated. A major gap in knowledge is the identification of the mechanisms underlying cognitive impairment in middle-age, and how modulating factors, such as exercise, could attenuate them.
The investigators propose that the composition of the gut microbiota and their metabolites in middle-age may predict reduced AHN and pattern separation, which may be rescued/improved by exercise, and is thus a key mechanistic target for investigation. In support, ageing is associated with a decline in gastrointestinal function and a change in microbiota composition. Middle-age is particularly vulnerable for gut microbiota compositional and metabolite changes coupled with neuroinflammation in mice, and that these effects are modified in response to prebiotic supplementation. An altered gut microbiota is associated with low mood/depressive behaviour through metabolic changes, and germ-free mice display an aberrant increase of neurogenesis. Moreover, preliminary data show that gut microbiota depletion (induced by long-term antibiotic administration) leads to a decrease in pattern separation and AHN, albeit in young adult rats.
Accumulating evidence suggests that exercise can change gut microbial composition and serum metabolites. Interestingly, human and rats present the same metabolic signature in plasma after exercise. Moreover, the effects of exercise on metabolic profiles are transmissible via faecal microbiota transplantation (FMT). Considering the gut microbiota (i) is sensitive to exercise and age, (ii) regulates AHN and, (iii) is involved in pattern separation and mood, the investigators propose that the gut microbiome-AHN communication is important in maintaining hippocampal integrity and cognitive function during middle-age.
Aim The overall aim of the NeuroFit study is to develop and test the impact of a group-based exercise intervention to identify specific gut microbiota and metabolic signatures that may influence cognitive and mood changes in middle-aged adults.
Hypothesis Reduced pattern separation in middle age can be rescued/improved by exercise accompanied by changes in the gut microbiota and related metabolites.
Objectives The NeuroFit study has 3 main objectives.
- Determine the impact of a 12-week exercise intervention (30 minutes, 3 days a week) compared to a control group (continued habitual behaviour) in healthy, middle-aged participants on cognition and mood.
- Identify specific gut microbiota and metabolic signatures in middle age which is responsive to exercise and predictive of cognitive and mood changes in a randomised controlled trial.
- Assess the impact of exercise on neuropsychiatric symptoms, serum BDNF, dietary intake, quality of life, habitual physical activity, cardio-respiratory fitness, anthropometry and cardiometabolic health on cognition and mood.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exercise | Experimental | Behavioral: Exercise12 weeks exercise intervention. 3 times a week, 45 minutes per session, 30 minutes of exercise. |
| Control | No intervention | –Continue with habitual routine. Take part in weekly online socials with others in the control group. |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 45 - 65 years of age.
- BMI 20 - 30.
- Does less than 90 minutes of moderate to vigorous physical activity per week and does not have a regular exercise routine(captured by self-reported measures)
Key exclusion criteria (30 listed)
- Subject is unable to understand the participant information sheet.
- Subject is unable to provide written informed consent.
- Subject is unable to understand and/or completely perform the cognitive testing.
- Impaired vision that is not corrected.
- Subject is a smoker.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exercise12 weeks of moderate intensity exercise, three times a week. | Behavioural | Exercise |
Primary outcome
Mnemonic Similarity Task
Time frame: Change from baseline pattern separation and recognition memory at 12 weeks
Pattern separation and recognition memory
Mnemonic Similarity Task
Time frame: Change from baseline pattern separation and recognition memory at 24 weeks
Pattern separation and recognition memory
13 secondary outcomes
Patient Health Questionnaire 9
Time frame: Change from baseline mood at 12 weeks
Patient Health Questionnaire 9
Time frame: Change from baseline mood at 24 weeks
Gut microbiome composition
Time frame: Change from baseline composition at 12 weeks
Metabolomic profile - Serum
Time frame: Change from baseline profile at 12 weeks
Metabolomic profile - Gut microbiota
Time frame: Change from baseline profile at 12 weeks
Short Form 12
Time frame: Change from baseline quality of life at 12 weeks
Short Form 12
Time frame: Change from baseline quality of life at 24 weeks
Cardiorespiratory fitness
Time frame: Change from baseline fitness at 12 weeks
Cardiorespiratory fitness
Time frame: Change from baseline fitness at 24 weeks
Bone derived neurotrophic factor (BDNF)
Time frame: Change from baseline BDNF levels at 12 weeks
Bone derived neurotrophic factor (BDNF)
Time frame: Change from baseline BDNF levels at 24 weeks
Nutritional intake
Time frame: Change from baseline nutritional intake at 12 weeks
Nutritional intake
Time frame: Change from baseline nutritional intake at 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2026.
- Derived from this study: PubMed 42754613Farmand S, Kim C, Du Preez A, Werneck AO, Batzu L, Pearce D, Brady K, Khir M, Nicolas S, Cryan JF, Nolan YM, Stubbs B, Thuret S. Effects of a three-month exercise programme on cognition, mood and neurogenesis: the NeuroFit randomised controlled trial. NPJ Aging. 2026 Sep 17;12(1):124. doi: 10.1038/s41514-026-00439-w.
- Individual participant dataSharing planned: Yes. Anonymised study data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sandrine Thuret, PhD principal investigator
King's College London
Brendon Stubbs, PhD principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise in people with Cognitive Decline, run by King's College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mnemonic Similarity Task (time frame: Change from baseline pattern separation and recognition memory at 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05397990, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2026.