The effect of bariatric surgery (RYGB or LSG) on central inflammation

Morbid Obesity

Morbidly obese subjects will receive either RYGB or LSG, and the effect of bariatric surgery-induced weight loss on brain inflammation will be assessed

Bariatric Surgery (RYGB or LSG)

Turku PET Centre

Turku University Hospital

Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, and Activation of Central Reward System

Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, Insulin Resistance and Activation of Central Reward System Studied Using PET- and MRI-imaging

Brain PET-[11C]-PK11195 imaging study of obese and healthy lean ones

PK11195 imaging results are compared before and 6 months after bariatric surgery in obese group studied before and after bariatric surgery

Glucose uptakes are measured using PET imaging in obese and leans

Comparison before and 6 months after surgery (obese group)

Comparison between obese and lean ones using fMRI

Comparison between obese baseline and 6 months after operation

MRS studies for obese and lean ones at baseline are compared

MRS studies for obese before and 6 months postop compared

Pirjo Nuutila

Professor

Obese and healthy ones are compared at baseline and obese are compered to healthy ones 6 months after bariatric surgery.

Participants who have a body mass index within the normal-weight category.

Participants who have a body mass index within the obese category.

Obesity

After 8 hours fasting overnight, an intravenous catheter is placed in the arm or hand for blood draws. Participants drink 75 grams of an oral glucose drink after baseline blood samples are drawn. More blood draws occur at 10, 20, 30, 60 and 120 min post-glucose drink.

Oral glucose tolerance test

For approximately 40 minutes, participants are assessed for cognitive function using computer-based tests available from the NIH Toolbox Cognitive Battery (Weintraub et al., 2013), including attention and executive functioning, episodic memory, working memory, language, processing speed, and immediate recall.

Cognitive testing

Magnetic resonance imaging (MRI) scans will be performed in a 3 Tesla MRI scanner over 1.5 hours. Participants will be asked to lay down flat on their backs and to try to stay still throughout the MRI scan. The participant will wear MRI-safe headphones to block out noise due to the MRI scans. Participant comfort will be verbally checked on throughout the scan and the participant will be provided with a 'squeeze ball' to signal the MRI technician that they want to get out of the scanner immediately.

Magnetic resonance imaging

NIH Toolbox Cognitive Battery description

Washington University School of Medicine

Cognition and Magnetic Resonance Imaging of Brain Inflammation in Obesity

Neuroinflammation in Obesity

Diffusion Basis Spectrum Imaging (Cross and Song, 2017) is a computational method that will be applied to diffusion tensor images of the brain to estimate putative inflammation-related markers including cellularity and edema in obese and normal-weight individuals. DBSI metrics are quantitative but unitless. Cellularity and edema fractions of the total diffusion signal (including axial, radial, restricted (cellularity) and hindered (edema)) will be estimated.

Cognitive performance including fluid and crystallized cognition composite T-scores from computer-based NIH Cognitive Toolbox assessments (Weintraub et al., 2013) will be assessed in obese and normal-weight individuals. These T-scores will include scores from tasks that assess attention and executive functioning, episodic memory, working memory, language, processing speed, and immediate recall (see NIH Toolbox Cognitive Battery website).

Plasma will be isolated from whole blood prior to the 2 hour oral glucose tolerance test (OGTT) and frozen for laboratory analyses. Peripheral inflammatory markers of interest including interleukin (IL)-6, IL-1B, total adiponectin, tumor necrosis factor alpha, C-C Motif Chemokine Ligand 2, toll receptor 4, and C-reactive protein will be measured using radioimmunoassay and enzyme-linked immunosorbent assays in a wet laboratory.

Plasma will be isolated from whole blood drawn at each OGTT time point and frozen. Insulin sensitivity and pancreatic beta function will be quantified using the oral glucose minimal model, which requires C-peptide, insulin, and glucose levels in plasma at fasting and throughout the 2 hour OGTT (Breda et al., 2001). Peripheral metabolic markers including C-peptide, insulin, and glucose levels in plasma will be measured for each timepoint of the OGTT using electrochemiluminescence, hexokinase ultraviolet method, and radioimmunoassay in a wet laboratory.

The project is still in early stages of recruiting and data collection.Data will be shared if it is included in a publication.

Sarah Eisenstein

Assistant Professor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment.

Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding.

The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment.
Recombinant human Growth Hormone: 400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements

Treatment With Recombinant Human Growth Hormone

Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding.
Placebo: SC injection daily

Placebo Treatment

Total

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

Baseline IGF-1 level < 1 SD below expected mean

Baseline L-Arginine stimulation test

Processing Speed Index ages standardized score. In this scale, higher scores represent better functioning, lower scores represent poorer function.
100 = mean of a normative population. 110 = 1 standard deviation above normal; 90 = 1 standard deviation below normal 120 = 2 standard deviations above normal; 80 = 2 standard deviations below normal

rhGH Treatment

Placebo Treament

Functional Outcome 6 Months After Injury, as Measured by the Processing Speed Index

Serum levels of Insulin-Like Growth Factor-1.

Active Treatment With Recombinant Human Growth Hormone

IGF-1 Levels.

Processing Speed Index 1 Year After Injury

Measurement of serum GH levels over 90 minutes after administration of L-arginine

GH Response to L-arginine Stimulation at Baseline

Serum IGF-1 levels at baseline for both treatment groups was correlated with the Processing Speed Index recorded at baseline, using Pearson's correlation coefficient. Perason's correlation coefficient is a measure of the linear correlation between two variables X and Y. It has a value between +1 and -1, where 1 is total positive linear correlation, 0 is no linear correlation, and -1 is total negative linear correlation.

IGF-1 Levels

Rates of diabetes mellitus, arthralgias, or peripheral edema between rhGH treatment and placebo.

Rates of Diabetes Mellitus, Arthralgias, or Peripheral Edema.

Overall Study

Ramon Diaz-Arrastia

Recombinant Human Growth Hormone

Traumatic Brain Injury

400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements

encephalitis/gojaznost

Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, and Activation of Central Reward System

Cognition and Magnetic Resonance Imaging of Brain Inflammation in Obesity

Recombinant Human Growth Hormone During Rehabilitation From Traumatic Brain Injury.

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