Impact of Metformin on Leptin Transport in Cerebrospinal Fluid of Obese Patients
- Conditions
- Obesity Without Type 2 Diabetes, With BMI>30
- Interventions
- Registration Number
- NCT03974139
- Lead Sponsor
- Lille Catholic University
- Brief 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. 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 31
- 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
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Obese patients Metformin Oral Tablet Patients with body mass index \>30
- Primary Outcome Measures
Name Time Method cerebrospinal fluid /plasma leptin ratio 3 months
- Secondary Outcome Measures
Name Time Method cerebrospinal fluid /plasma insulin ratio 3 months Cerebrospinal fluid levels of neuropeptide Y (NPY) at day 0, 3 months Plasma levels of leptin soluble receptor at day 0, 3 months cerebrospinal fluid /plasma glucose ratio at day 0, 3 months Cerebrospinal fluid levels of Agouti-Related Peptide (AgRP) at day 0, 3 months Plasma levels of neuropeptide Y (NPY) at day 0, 3 months Hypothalamic concentration of creatine at day 0, 3 months This concentration will be measure by spectroscopy
Abdominal circumference 3 months cerebrospinal fluid /plasma glucagon like peptide 1 (GLP1) ratio at day 0, 3 months cerebrospinal fluid /plasma ghrelin ratio at day 0, 3 months Plasma levels of Agouti-Related Peptide (AgRP) at day 0, 3 months Cerebrospinal fluid levels of proopiomelanocortin (POMC) at day 0, 3 months Plasma levels of proopiomelanocortin (POMC) at day 0, 3 months Cerebrospinal fluid levels of leptin soluble receptor at day 0, 3 months Apparent diffusion coefficient (ADC) at day 0, 3 months 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
Hypothalamic concentration of N-acetyl-aspartate (NAA) at day 0, 3 months This concentration will be measure by spectroscopy
Hypothalamic concentration of gamma-aminobutyric acid (GABA) at day 0, 3 months This concentration will be measure by spectroscopy
Percentage of body fat at day 0, 3 months 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.
Energy expenditure at day 0, 3 months This parameter will measure by indirect calorimetry (kCal / 24h)
Hypothalamic concentration of Choline 3 months This concentration will be measure by spectroscopy
Hypothalamic concentration of Glutamine / glutamate at day 0, 3 months This concentration will be measure by spectroscopy
Weight at day 0, 3 months Score of the Three Factor Eating Questionnaire (TFEQ) 3 months 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 21-16-14Score of the Dutch Eating Behaviour Questionnaire (DEBQ) at day 0, 3 months 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.
Fat free mass (Kg) at day 0, 3 months 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.
Trial Locations
- Locations (1)
Centre hospitalier d'Arras
🇫🇷Arras, France