Obesity Without Type 2 Diabetes, With BMI>30Phase 2LEPTOBNCT03974139
Impact of Metformin on Leptin Transport in Cerebrospinal Fluid of Obese Patients
A Phase 2 study testing Metformin Oral Tablet in people with Obesity Without Type 2 Diabetes, With BMI>30, run by Lille Catholic University at 1 site in France.
Trial summary
Obesity, a major health problem, is gradually transforming into a global epidemic. The current obesity treatment with long term efficacy is the bariatric surgery, however, the operative risk of this procedure is high and the post-operative iotrogeny may be important. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Obesity Without Type 2 Diabetes, With BMI>30
- What is being tested?
- Metformin Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteFrance
- Study dates
- 3 Jul 2020to 30 Sep 2024
- Phase
- Phase 2
- 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 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Adults between 18 and 40 years old
- Body mass index >30
- For childbearing age women: use of an effective contraceptive method for the duration of the study
- Patients willing to participate in the study and who have signed the informed consent form
- Patients with health insurance
Who cannot join
- Genetic obesity
- Type 2 diabetes defined by 2 fasting blood glucose >1,26g/L or blood glucose >2 g/L at 120 min of oral glucose tolerance test with 75 g of glucose
- Patients already treated with metformin
- Type 1 diabetes
- Active neoplastic pathology, diagnosed < 5 years, or in treatment
- Neurological pathology (demyelinating, tumor, vascular)
Show all 16Show fewer
- Adipose tissue pathology (lipodystrophy)
- History of bariatric surgery
- Contraindication to metformin
- Lumbar puncture contraindication
- MRI contraindication
- Person unable to consent, or benefiting from a legal protection regime (guardianship/curatorship/guardianship of justice)
- Pregnant or breastfeeding woman
- Contra-indication to impedance measurement
- Contraindication to indirect calorimetry: claustrophobia
- Taking a psychotropic drug
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Centre hospitalier d'Arras
Arras, 62022
Vincent Florent, MD, MSc, PhD
About this study
Official title: Study of the Communication of the Hypothalamus With the Periphery: Impact of Metformin on Leptin Transport in the Cerebrospinal Fluid of Obese Patients. A Monocentric Prospective Study
Obesity, a major health problem, is gradually transforming into a global epidemic. The current obesity treatment with long term efficacy is the bariatric surgery, however, the operative risk of this procedure is high and the post-operative iotrogeny may be important. Obesity is most often associated to the feeding behavior which depends on hypothalamic integration of peripheral signals such as leptin and glucose. High levels of circulating leptin are detected in obese patients. These elevated leptin levels fail to reduce appetite or increase energy expenditure. The mechanism underlying this non-integration of peripheral signals remains to be identified. The ratio of leptin levels in the cereprospinal fluid (CSF) and in the periphery is drastically decreased in obese patients when compared to lean individuals, therefore a defective transport of circulating leptin into the brain via the CSF is maybe linked to obesity.
Read the detailed description
We hypothesize that the alteration of leptin transport into the CSF of obese patients could be modulated by drugs such as metformin which is widely used worldwide to treat diabetes. This study is monocentric, prospective, one-arm type and interventional. The main objective isto evaluate the impact of metformin on the transport of leptin into the CSF of obese patients.
We propose to show a variation of CSF leptin / serum leptin before and after metformin treatment and study its association with changes in hypothalamic metabolic activity, cognitive and appetite-related behaviors and ratio of other metabolic signals. This would support the hypothesis of modulation of resistance to peripheral leptin by metformin and thus uncover a new indication for metformin treatment towards the management of obesity.
For this purpose, volunteers will be subjected to blood sampling via venipuncture, CSF collection via lumbar puncture, MRI assessments and questionnaires (cognitive tests, food survey and feeding behavior) before and after a 3-month metformin treatment.
- Being tested
- Metformin Oral Tablet
- Keywords
- metformin, leptin, cerebrospinal fluid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin Oral TabletDrug
Day 1 to day 3: 500 mg/day Day 4 to day 6: 500 mg/twice a day Day 7 to day 9: 500 mg three times a day Day 10 until next lumbar puncture : 850 mg three times a day
| Study group | Role | What they receive |
|---|---|---|
| Obese patients | Experimental | Patients with body mass index >30 Receives: Drug: Metformin Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
cerebrospinal fluid /plasma leptin ratio
Measured: 3 months
Secondary outcomes (25)
cerebrospinal fluid /plasma glucose ratio
Measured: at day 0, 3 months
cerebrospinal fluid /plasma glucagon like peptide 1 (GLP1) ratio
Measured: at day 0, 3 months
cerebrospinal fluid /plasma insulin ratio
Measured: 3 months
cerebrospinal fluid /plasma ghrelin ratio
Measured: at day 0, 3 months
Cerebrospinal fluid levels of Agouti-Related Peptide (AgRP)
Measured: at day 0, 3 months
Plasma levels of Agouti-Related Peptide (AgRP)
Measured: at day 0, 3 months
Cerebrospinal fluid levels of proopiomelanocortin (POMC)
Measured: at day 0, 3 months
Plasma levels of proopiomelanocortin (POMC)
Measured: at day 0, 3 months
Cerebrospinal fluid levels of neuropeptide Y (NPY)
Measured: at day 0, 3 months
Plasma levels of neuropeptide Y (NPY)
Measured: at day 0, 3 months
Cerebrospinal fluid levels of leptin soluble receptor
Measured: at day 0, 3 months
Plasma levels of leptin soluble receptor
Measured: at day 0, 3 months
Apparent diffusion coefficient (ADC)
Apparent diffusion coefficient (ADC) is a measure of the magnitude of diffusion (of water molecules) within tissue, and is commonly clinically calculated using Magnetic resonance imaging (MRI). An ADC of a tissue is expressed in units of mm2/s
Measured: at day 0, 3 months
Hypothalamic concentration of N-acetyl-aspartate (NAA)
This concentration will be measure by spectroscopy
Measured: at day 0, 3 months
Hypothalamic concentration of creatine
This concentration will be measure by spectroscopy
Measured: at day 0, 3 months
Hypothalamic concentration of Choline
This concentration will be measure by spectroscopy
Measured: 3 months
Hypothalamic concentration of Glutamine / glutamate
This concentration will be measure by spectroscopy
Measured: at day 0, 3 months
Hypothalamic concentration of gamma-aminobutyric acid (GABA)
This concentration will be measure by spectroscopy
Measured: at day 0, 3 months
Weight
Measured: at day 0, 3 months
Abdominal circumference
Measured: 3 months
Percentage of body fat
This parameter will measure by bioelectrical impedance analysis (BIA). A weak electric current flows through the body and the voltage is measured in order to calculate impedance (resistance) of the body.
Measured: at day 0, 3 months
Fat free mass (Kg)
This parameter will measure by bioelectrical impedance analysis (BIA). A weak electric current flows through the body and the voltage is measured in order to calculate impedance (resistance) of the body.
Measured: at day 0, 3 months
Energy expenditure
This parameter will measure by indirect calorimetry (kCal / 24h)
Measured: at day 0, 3 months
Score of the Three Factor Eating Questionnaire (TFEQ)
The TFEQ contains 51 items and measures three dimensions of eating behavior:
- cognitive restraint of eating' (Factor I - 21 items)
- disinhibition (Factor II - 16 items)
- hunger (Factor III - 14 items)
Each item scores either 0 or 1 point. The minimum score for factors I-II-III is therefore 0-0-0, the possible maximum score 21-16-14
Measured: 3 months
Score of the Dutch Eating Behaviour Questionnaire (DEBQ)
This is a 33-item self-report questionnaire to assess three distinct eating behaviors in adults: (1) emotional eating, (2) external eating, and (3) restrained eating. Items on the DEBQ range from 1 (never) to 5 (very often), with higher scores indicating greater endorsement of the eating behavior.
Measured: at day 0, 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2019
- Study start3 Jul 2020
- Primary completion15 Jun 2024 (estimated)
- Study completion30 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obesity Without Type 2 Diabetes, With BMI>30Studies 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 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lille Catholic University
- Sponsor type
- University, hospital or other
- Collaborators
- Centre Hospitalier Arras
- Responsible party
- Sponsor
- Investigators
- Vincent Prévot, PhD, Study director, Institut National de la Santé Et de la Recherche Médicale, FranceVincent Florent, MD, MSc, PhD, Principal investigator, Centre Hospitalier d'Arras, INSERM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03974139
- Sponsor's protocol ID
- RC-P0054
- Acronym
- LEPTOB
- Status last verified
- Oct 2023
- First submitted
- 28 May 2019
- Last updated
- 31 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Communication of the Hypothalamus With the Periphery: Impact of Metformin on Leptin Transport in the Cerebrospinal Fluid of Obese Patients. A Monocentric Prospective Study
- ClinicalTrials.gov ID
- NCT03974139
- Acronym / sponsor ID
- LEPTOB / RC-P0054
- Keywords
- metformin, leptin, cerebrospinal fluid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 31 participants (estimated)
- Lead sponsor
- Lille Catholic UniversityUniversity, hospital or other
- Collaborators
- Centre Hospitalier Arras
- Study start
- 3 Jul 2020 (actual)
- Primary completion
- 15 Jun 2024 (estimated)
- Study completion
- 30 Sep 2024 (estimated)
- First posted
- 4 Jun 2019 (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.
Obesity, a major health problem, is gradually transforming into a global epidemic. The current obesity treatment with long term efficacy is the bariatric surgery, however, the operative risk of this procedure is high and the post-operative iotrogeny may be important. Obesity is most often associated to the feeding behavior which depends on hypothalamic integration of peripheral signals such as leptin and glucose. High levels of circulating leptin are detected in obese patients. These elevated leptin levels fail to reduce appetite or increase energy expenditure. The mechanism underlying this non-integration of peripheral signals remains to be identified. The ratio of leptin levels in the cereprospinal fluid (CSF) and in the periphery is drastically decreased in obese patients when compared to lean individuals, therefore a defective transport of circulating leptin into the brain via the CSF is maybe linked to obesity.
Detailed description
We hypothesize that the alteration of leptin transport into the CSF of obese patients could be modulated by drugs such as metformin which is widely used worldwide to treat diabetes. This study is monocentric, prospective, one-arm type and interventional. The main objective isto evaluate the impact of metformin on the transport of leptin into the CSF of obese patients.
We propose to show a variation of CSF leptin / serum leptin before and after metformin treatment and study its association with changes in hypothalamic metabolic activity, cognitive and appetite-related behaviors and ratio of other metabolic signals. This would support the hypothesis of modulation of resistance to peripheral leptin by metformin and thus uncover a new indication for metformin treatment towards the management of obesity.
For this purpose, volunteers will be subjected to blood sampling via venipuncture, CSF collection via lumbar puncture, MRI assessments and questionnaires (cognitive tests, food survey and feeding behavior) before and after a 3-month metformin treatment.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Obese patients | Experimental | Drug: Metformin Oral TabletPatients with body mass index >30 |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Adults between 18 and 40 years old
- Body mass index >30
- For childbearing age women: use of an effective contraceptive method for the duration of the study
- Patients willing to participate in the study and who have signed the informed consent form
- Patients with health insurance
Key exclusion criteria (16 listed)
- Genetic obesity
- Type 2 diabetes defined by 2 fasting blood glucose >1,26g/L or blood glucose >2 g/L at 120 min of oral glucose tolerance test with 75 g of glucose
- Patients already treated with metformin
- Type 1 diabetes
- Active neoplastic pathology, diagnosed < 5 years, or in treatment
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 |
|---|---|---|
| Metformin Oral TabletDay 1 to day 3: 500 mg/day Day 4 to day 6: 500 mg/twice a day Day 7 to day 9: 500 mg three times a day Day 10 until next lumbar puncture : 850 mg three times a day | Drug | Obese patients |
Primary outcome
cerebrospinal fluid /plasma leptin ratio
Time frame: 3 months
25 secondary outcomes
cerebrospinal fluid /plasma glucose ratio
Time frame: at day 0, 3 months
cerebrospinal fluid /plasma glucagon like peptide 1 (GLP1) ratio
Time frame: at day 0, 3 months
cerebrospinal fluid /plasma insulin ratio
Time frame: 3 months
cerebrospinal fluid /plasma ghrelin ratio
Time frame: at day 0, 3 months
Cerebrospinal fluid levels of Agouti-Related Peptide (AgRP)
Time frame: at day 0, 3 months
Plasma levels of Agouti-Related Peptide (AgRP)
Time frame: at day 0, 3 months
Cerebrospinal fluid levels of proopiomelanocortin (POMC)
Time frame: at day 0, 3 months
Plasma levels of proopiomelanocortin (POMC)
Time frame: at day 0, 3 months
Cerebrospinal fluid levels of neuropeptide Y (NPY)
Time frame: at day 0, 3 months
Plasma levels of neuropeptide Y (NPY)
Time frame: at day 0, 3 months
Cerebrospinal fluid levels of leptin soluble receptor
Time frame: at day 0, 3 months
Plasma levels of leptin soluble receptor
Time frame: at day 0, 3 months
Apparent diffusion coefficient (ADC)
Time frame: at day 0, 3 months
Hypothalamic concentration of N-acetyl-aspartate (NAA)
Time frame: at day 0, 3 months
Hypothalamic concentration of creatine
Time frame: at day 0, 3 months
Hypothalamic concentration of Choline
Time frame: 3 months
Hypothalamic concentration of Glutamine / glutamate
Time frame: at day 0, 3 months
Hypothalamic concentration of gamma-aminobutyric acid (GABA)
Time frame: at day 0, 3 months
Weight
Time frame: at day 0, 3 months
Abdominal circumference
Time frame: 3 months
Percentage of body fat
Time frame: at day 0, 3 months
Fat free mass (Kg)
Time frame: at day 0, 3 months
Energy expenditure
Time frame: at day 0, 3 months
Score of the Three Factor Eating Questionnaire (TFEQ)
Time frame: 3 months
Score of the Dutch Eating Behaviour Questionnaire (DEBQ)
Time frame: at day 0, 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2023.
- Individual participant dataSharing planned: Undecided
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.
Vincent Prévot, PhD study director
Institut National de la Santé Et de la Recherche Médicale, France
Vincent Florent, MD, MSc, PhD principal investigator
Centre Hospitalier d'Arras, INSERM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin Oral Tablet in people with Obesity Without Type 2 Diabetes, With BMI>30, run by Lille Catholic University at 1 site in France.
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 5 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 31 Oct 2023. 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 France. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Amélie Lansiaux, MD, PhD (0033320225741, lansiaux.amelie@ghcl.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cerebrospinal fluid /plasma leptin ratio (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Oct 2023.