ObesityNCT04453150
Microbiota in Dietary Approach to Obesity
A study testing Standard hypocaloric die, Intermittent fasting 16/8 (early fasting) and Intermittent fasting 16/8 (late fasting) in people with Obesity, run by Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud at 1 site in Spain.
Trial summary
Main aim: Study the anthropometric, metabolic, cardiovascular and neurocognitive and gut microbiota changes of different approaches for the weight reduction that increase the ketone bodies in a different proportion in relation to the classic hypocaloric diet. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- Standard hypocaloric die, Intermittent fasting 16/8 (early fasting) and Intermittent fasting 16/8 (late fasting)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteSpain
- Study dates
- 22 Jan 2020to 22 Jun 2022
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Obesity (BMI≥30-45 kg/m2)
Who cannot join
- Type 2 diabetes mellitus
- Patients with major cardiovascular events in the 6 months prior to the study beginning.
- Previous or current history of inflammatory disease.
- Active infectious disease.
- The refusal of the patient to participate in the study
- Consumption of probiotics or prebiotics
- Antibiotic therapy in the 3 months prior to the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ketone Bodies and Gut Microbiota Role in the Dietetic Approach of Obesity
Main aim: Study the anthropometric, metabolic, cardiovascular and neurocognitive and gut microbiota changes of different approaches for the weight reduction that increase the ketone bodies in a different proportion in relation to the classic hypocaloric diet.
Objective 1: Study the effect of hypocaloric diets that increase the ketone bodies on gut microbiota and its relationship with anthropometric changes and of the Brown adipose tissue, Objective 2: with the metabolic and inflammatory changes, Objective 3: on the cardiovascular system, Objective 4: on the neurocognition, Objective 5: if they are associated to epigenetic changes that may explain the changes found in the other objectives. Objective 6: Determine the safety of the diets that increase the ketone bodies compared to the classic hypocaloric diet, Objective 7: if the effects of the different dietary approaches are maintained during the medium time, and Objective 8: Verify in experimental models (microbiota transplants from humans with different diets to germ-free mice, ketosis dietary models, and ketone bodies administration) the causality of the gut microbiota of these findings.
Methodology: Model 1: Dietary intervention in humans with 4 types of diet with a different increase of the ketone bodies: classic hypocaloric diet (DH); diet with 8h of feeding and 16h of starving in periods of 24h (D16); diet with intermittent caloric restriction (DA); and normal in protein and low in carbohydrates hypocaloric ketogenic diet (DC).
- Conditions
- Obesity
- Being tested
- Standard hypocaloric die, Intermittent fasting 16/8 (early fasting), Intermittent fasting 16/8 (late fasting), Alternate-day fasting, Ketogenic diet
- Keywords
- Ketosis, Microbiota
- Medical subject headings
- Obesity, Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard hypocaloric dieOther
Standard hypocaloric diet
Intermittent fasting 16/8 (early fasting)Other
Intermittent fasting 16/8 (early fasting)
Intermittent fasting 16/8 (late fasting)Other
Intermittent fasting 16/8 (late fasting)
Alternate-day fastingOther
Alternate-day fasting
Ketogenic dietOther
Ketogenic diet
| Study group | Role | What they receive |
|---|---|---|
| Standard hypocaloric diet | Experimental | Mediterranean diet based on olive oil as main fat and regular consumption of vegetables (2 daily rations), fruits 3 daily rations), legumes (3 weekly rations), fish (3 weekly rations), with low consumption of red meat and meat products (less than twice a week), dairy foods (less than once a week) and no sweets, pastries or sugary drinks. Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein distributed in at least 4 meals (breakfast, lunch, afternoon snack and dinner). Receives: Other: Standard hypocaloric die |
| Intermittent fasting 16/8 (early fasting) | Experimental | Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein, but it will be consumed for 8 hours a day (from 12 am. to 8 pm.), maintaining 16 fasting hours (from 8 pm. to 12 am. the following day). Receives: Other: Intermittent fasting 16/8 (early fasting) |
| Intermittent fasting 16/8 (late fasting) | Experimental | Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein, but it will be consumed for 8 hours a day (from 8 am. to 4 pm.), maintaining 16 fasting hours (from 4 pm. to 8 am. the following day). Receives: Other: Intermittent fasting 16/8 (late fasting) |
| Alternate-day fasting | Experimental | In this diet subjects alternate norm caloric diet during 24 h (according to Harris-Benedict equation) and a diet including only 25% of caloric requirements the following 24 h (this day diet will include 5 % carbohydrates, 65% fat and 30% high biological value protein). Receives: Other: Alternate-day fasting |
| Ketogenic diet | Experimental | Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 5 % carbohydrates, 65% fat and 30% high biological value protein. Receives: Other: Ketogenic diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in gut microbiota composition
To evaluate changes in gut microbiota composition from baseline using different strategies for weight loss which increase ketone bodies in comparison to a standard hypocaloric diet. Change from baseline in 16S rRNA amplicons of fecal community DNA at 3 months and 6 months
Measured: Baseline, 12 weeks
Secondary outcomes (10)
Changes in weight
To analyze the effect of hypocaloric diets which increase ketone bodies on anthropometric parameters in comparison to a standard hypocaloric diet
Measured: Baseline, 12 weeks
Changes in body mass index.
To analyze the effect of hypocaloric diets which increase ketone bodies on body mass index in comparison to a standard hypocaloric diet
Measured: Baseline, 12 weeks
Changes in waist circumference.
To analyze the effect of hypocaloric diets which increase ketone bodies on the waist circumference in comparison to a standard hypocaloric diet
Measured: Baseline, 12 weeks
Changes in body composition.
To analyze the effect of hypocaloric diets which increase ketone bodies on anthropometric parameters in comparison to a standard hypocaloric diet measured by bioelectrical impedance analysis
Measured: Baseline, 12 weeks
Changes in brown adipose tissue.
To analyze the effect of hypocaloric diets which increase ketone bodies on brown adipose tissue in comparison to a standard hypocaloric diet, measured by Positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET).
Measured: Baseline, 12 weeks
Changes in uncoupling protein 1 (UCP1)
To analyze the effect of hypocaloric diets which increase ketone bodies on brown adipose tissue UCP1 in comparison to a standard hypocaloric diet using a sample of subcutaneous white adipose tissue assessed by mRNA qPCR.
Measured: Baseline, 12 weeks
Changes in physical activity.
To analyze the effect of hypocaloric diets which increase ketone bodies on physical activity in comparison to a standard hypocaloric diet measured by accelerometry
Measured: Baseline, 12 weeks
Changes in blood pressure
To analyze the effect of hypocaloric diets which increase ketone bodies over the cardiovascular system in comparison to a standard hypocaloric diet based on blood pressure
Measured: Baseline, 12 weeks
Changes in the punctuation in neurocognitive test
To analyze the effect of hypocaloric diets which increase ketone bodies on neurocognition, in comparison to a standard hypocaloric diet, measured by neurocognitive test
Measured: Baseline, 12 weeks
Changes in heart rate
To analyze the effect of hypocaloric diets which increase ketone bodies on heart function measured by heart rate in comparison to a standard hypocaloric diet, measured by Holter.
Measured: Baseline, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2020
- Study start22 Jan 2020
- Primary completion9 Jun 2022
- Study completion22 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Francisco J. Tinahones, PhD, Principal investigator, Instituto de Investigacion Biomedica de Malaga
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04453150
- Sponsor's protocol ID
- ISCIII CP18/01160
- Status last verified
- Jul 2021
- First submitted
- 17 Apr 2020
- Last updated
- 6 Jul 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Martinez-Montoro JI, Bandera B, Gutierrez-Bedmar M, Gomez-Perez AM, Macias-Gonzalez M, Moreno-Indias I, Tinahones FJ. Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial. BMC Med. 2025 Jul 1;23(1):368. doi: 10.1186/s12916-025-04182-z.
PubMed 40598397Mela V, Heras V, Iesmantaite M, Garcia-Martin ML, Bernal M, Posligua-Garcia JD, Subiri-Verdugo A, Martinez-Montoro JI, Gomez-Perez AM, Bandera B, Moreno-Indias I, Tinahones FJ. Microbiota fasting-related changes ameliorate cognitive decline in obesity and boost ex vivo microglial function through the gut-brain axis. Gut. 2025 Oct 8;74(11):1828-1846. doi: 10.1136/gutjnl-2025-335353.
PubMed 40335161
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketone Bodies and Gut Microbiota Role in the Dietetic Approach of Obesity
- ClinicalTrials.gov ID
- NCT04453150
- Acronym / sponsor ID
- ISCIII CP18/01160
- Conditions
- Obesity
- Keywords
- Ketosis, Microbiota
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y SaludUniversity, hospital or other
- Study start
- 22 Jan 2020 (actual)
- Primary completion
- 9 Jun 2022 (actual)
- Study completion
- 22 Jun 2022 (actual)
- First posted
- 1 Jul 2020 (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.
Main aim: Study the anthropometric, metabolic, cardiovascular and neurocognitive and gut microbiota changes of different approaches for the weight reduction that increase the ketone bodies in a different proportion in relation to the classic hypocaloric diet.
Objective 1: Study the effect of hypocaloric diets that increase the ketone bodies on gut microbiota and its relationship with anthropometric changes and of the Brown adipose tissue, Objective 2: with the metabolic and inflammatory changes, Objective 3: on the cardiovascular system, Objective 4: on the neurocognition, Objective 5: if they are associated to epigenetic changes that may explain the changes found in the other objectives. Objective 6: Determine the safety of the diets that increase the ketone bodies compared to the classic hypocaloric diet, Objective 7: if the effects of the different dietary approaches are maintained during the medium time, and Objective 8: Verify in experimental models (microbiota transplants from humans with different diets to germ-free mice, ketosis dietary models, and ketone bodies administration) the causality of the gut microbiota of these findings.
Methodology: Model 1: Dietary intervention in humans with 4 types of diet with a different increase of the ketone bodies: classic hypocaloric diet (DH); diet with 8h of feeding and 16h of starving in periods of 24h (D16); diet with intermittent caloric restriction (DA); and normal in protein and low in carbohydrates hypocaloric ketogenic diet (DC).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Standard hypocaloric diet | Experimental | Other: Standard hypocaloric dieMediterranean diet based on olive oil as main fat and regular consumption of vegetables (2 daily rations), fruits 3 daily rations), legumes (3 weekly rations), fish (3 weekly rations), with low consumption of red meat and meat products (less than twice a week), dairy foods (less than once a week) and no sweets, pastries or sugary drinks. Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein distributed in at least 4 meals (breakfast, lunch, afternoon snack and dinner). |
| Intermittent fasting 16/8 (early fasting) | Experimental | Other: Intermittent fasting 16/8 (early fasting)Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein, but it will be consumed for 8 hours a day (from 12 am. to 8 pm.), maintaining 16 fasting hours (from 8 pm. to 12 am. the following day). |
| Intermittent fasting 16/8 (late fasting) | Experimental | Other: Intermittent fasting 16/8 (late fasting)Diet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 45% carbohydrates, 35% fat, 20% protein, but it will be consumed for 8 hours a day (from 8 am. to 4 pm.), maintaining 16 fasting hours (from 4 pm. to 8 am. the following day). |
| Alternate-day fasting | Experimental | Other: Alternate-day fastingIn this diet subjects alternate norm caloric diet during 24 h (according to Harris-Benedict equation) and a diet including only 25% of caloric requirements the following 24 h (this day diet will include 5 % carbohydrates, 65% fat and 30% high biological value protein). |
| Ketogenic diet | Experimental | Other: Ketogenic dietDiet will produce a 600 kcal per day caloric deficit, according to the Harris-Benedict equation for each subject. Diet will include 5 % carbohydrates, 65% fat and 30% high biological value protein. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Obesity (BMI≥30-45 kg/m2)
Key exclusion criteria (7 listed)
- Type 2 diabetes mellitus
- Patients with major cardiovascular events in the 6 months prior to the study beginning.
- Previous or current history of inflammatory disease.
- Active infectious disease.
- The refusal of the patient to participate in the study
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 |
|---|---|---|
| Standard hypocaloric dieStandard hypocaloric diet | Other | Standard hypocaloric diet |
| Intermittent fasting 16/8 (early fasting)Intermittent fasting 16/8 (early fasting) | Other | Intermittent fasting 16/8 (early fasting) |
| Intermittent fasting 16/8 (late fasting)Intermittent fasting 16/8 (late fasting) | Other | Intermittent fasting 16/8 (late fasting) |
| Alternate-day fastingAlternate-day fasting | Other | Alternate-day fasting |
| Ketogenic dietKetogenic diet | Other | Ketogenic diet |
Primary outcome
Changes in gut microbiota composition
Time frame: Baseline, 12 weeks
To evaluate changes in gut microbiota composition from baseline using different strategies for weight loss which increase ketone bodies in comparison to a standard hypocaloric diet. Change from baseline in 16S rRNA amplicons of fecal community DNA at 3 months and 6 months
10 secondary outcomes
Changes in weight
Time frame: Baseline, 12 weeks
Changes in body mass index.
Time frame: Baseline, 12 weeks
Changes in waist circumference.
Time frame: Baseline, 12 weeks
Changes in body composition.
Time frame: Baseline, 12 weeks
Changes in brown adipose tissue.
Time frame: Baseline, 12 weeks
Changes in uncoupling protein 1 (UCP1)
Time frame: Baseline, 12 weeks
Changes in physical activity.
Time frame: Baseline, 12 weeks
Changes in blood pressure
Time frame: Baseline, 12 weeks
Changes in the punctuation in neurocognitive test
Time frame: Baseline, 12 weeks
Changes in heart rate
Time frame: Baseline, 12 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 6 Jul 2022.
- Derived from this study: PubMed 40598397Martinez-Montoro JI, Bandera B, Gutierrez-Bedmar M, Gomez-Perez AM, Macias-Gonzalez M, Moreno-Indias I, Tinahones FJ. Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial. BMC Med. 2025 Jul 1;23(1):368. doi: 10.1186/s12916-025-04182-z.
- Derived from this study: PubMed 40335161Mela V, Heras V, Iesmantaite M, Garcia-Martin ML, Bernal M, Posligua-Garcia JD, Subiri-Verdugo A, Martinez-Montoro JI, Gomez-Perez AM, Bandera B, Moreno-Indias I, Tinahones FJ. Microbiota fasting-related changes ameliorate cognitive decline in obesity and boost ex vivo microglial function through the gut-brain axis. Gut. 2025 Oct 8;74(11):1828-1846. doi: 10.1136/gutjnl-2025-335353.
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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.
Francisco J. Tinahones, PhD principal investigator
Instituto de Investigacion Biomedica de Malaga
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standard hypocaloric die, Intermittent fasting 16/8 (early fasting) and Intermittent fasting 16/8 (late fasting) in people with Obesity, run by Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud at 1 site in Spain.
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 1 inclusion and 7 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 6 Jul 2022. 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 Spain. 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?
Changes in gut microbiota composition (time frame: Baseline, 12 weeks). 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 NCT04453150, which also lists 2 linked publications.
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 6 Jul 2022.