Natriuretic Effect of GLP-1in Healthy Non Obese Subjects
कीवर्ड
सार
विवरण
This is a cross-over study. Totally 15 participants will be randomized (or other number later determined by power test). The duration of the study is 9 days that will include 3 visits and screening visit before starting the study.
Screening (day -1) Inclusion criteria are fulfilled before approaching Visit 1 on screening. Participants are instructed do come next day fasting and to collect 24h of urine sample.
Visit 1 (day 1) Participant voluntarily agrees to participate by giving informed written consent. Baseline study assessment is going to be performed fasting: blood count and differential, blood chemistry (liver enzymes, sodium, potassium, calcium, phosphorus, magnesium, chloride, serum amorality, urea and creatinine, lipid panel including cholesterol, triglycerides, HDL and LDL cholesterol, coagulation, uric acid, glucose and insulin, renin activity, aldosterone, GLP1 level, T4 TSH-thyroid stimulating hormone, ADH, BNP) In the 24 h urine collection sodium, chloride and calcium excretion, osmolality, creatinine are going to be measured, glomerular filtration is going to be assessed by creatinine clearance, urin analysis with microscopy is going to be preformed, EKG, kidney ultrasound together with 24-h blood pressure monitor. HOMA2 (The Homeostasis Model Assessment ) index is calculated and a total body water percentage determinated via Bioelectrical Impedance Analysis. All samples of renin activity and aldosterone in a study are going to be taken while being in horizontal position at least for 3 hours. Participants are going to be randomized regarding the glucose tolerance test. First group it the one with fasting glucose 4,5 -5,7 mmol/L and at 2 hour OGTT (the amount of sodium in OGTT fluid used is 0,4 mg of sodium and 0,3 mg of chloride in 0,2 L of water) glucose level below 7.8 mmol/l. The other group is the one with fasting glucose from 5,7 to 7 mmol/l and/or at 2 hour OGTT glucose level form 7.8 mmol/l to 11,1 mmol/L (venous sample). Patients are instructed to come on the next day fasting again.
Visit 2 (day 2) is a next study assessment: 24-h blood pressure monitor is removed, after the overnight fast oral saline load is going to be given in a form of a standardized meal (soup) in a amount of 12 g of NaCl (average daily intake of salt in Croatia). The soup is going to be consumed in 30 minutes. Volunteers are going to be instructed to drink afterwards 1/2 L of water during next 1 h. Placebo in a form iv infusion of hypertonic saline is going to be given at a rate of 0.06 ml/kg/in and infused during 3 hours from beginning of oral sodium load. During 6 hours (from oral sodium load) urine is gong to be collected. Finally, blood samples are going to be drawn for glucose, insulin, sodium, potassium, serum osmolality, serum creatinine, renin activity, and aldosterone, BNP, ADH and GLP1 level after 3 and 6 hours. Sodium, chloride and calcium excretion, osmolality and creatinine are going to be measured in the urine after 3 hours. Patients are instructed to come again after 7 days fasting.
Visit 3 (day 9) after the overnight fast again oral sodium load is going to be given in a form of a standardized meal (soup) in a same amount as previous day and again consumed in 30 minutes, they are going to drink afterwards 1/2 L of water during next 1 h like pervious day. Synthetic GLP-1 (1.5 pmol/kg/min) dissolved in 500 ml 0.9% saline is going to be infused during 3 hours from beginning of oral sodium load. During 6 hours (from oral sodium load) urine is gong to be collected, blood samples are going to be drawn after 3 and 6 hours for the same analysis as in Visit 2, just like urine collection after 6 hours.
खजूर
| अंतिम सत्यापित: | 11/30/2015 |
| पहले प्रस्तुत किया गया: | 04/28/2014 |
| अनुमानित नामांकन प्रस्तुत किया गया: | 04/30/2014 |
| पहले पोस्ट किया गया: | 05/04/2014 |
| अंतिम अद्यतन प्रस्तुत किया: | 12/10/2015 |
| अंतिम अद्यतन पोस्ट: | 12/13/2015 |
| वास्तविक अध्ययन प्रारंभ दिनांक: | 03/31/2014 |
| अनुमानित प्राथमिक समापन तिथि: | 09/30/2015 |
| अनुमानित अध्ययन पूर्णता तिथि: | 09/30/2015 |
स्थिति या रोग
हस्तक्षेप / उपचार
Drug: Saline infusion with GLP1
Other: Saline infusion
चरण
शाखा समूह
| बांह | हस्तक्षेप / उपचार |
|---|---|
| Active Comparator: Saline infusion infusion of saline | Other: Saline infusion infusion of saline |
| Active Comparator: Saline infusion with GLP1 infusion of saline with GLP1 | Drug: Saline infusion with GLP1 infusion of synthetic GLP-1 (1.5 pmol/kg/min) saline |
पात्रता मापदंड
| युग अध्ययन के लिए पात्र | 18 Years सेवा 18 Years |
| सेक्स अध्ययन के लिए पात्र | All |
| स्वस्थ स्वयंसेवकों को स्वीकार करता है | हाँ |
| मानदंड | Inclusion Criteria: Inclusion criteria: - Participant is ≥18 and ≤70 years of age on day of signing informed consent - Participant is a male, or a female who is unlikely to conceive, as indicated by at least one "yes" answer to the following questions: - Patient is a surgically sterilized female - Patient is a postmenopausal female ≥45 years of age with >2 years since last menses - Patient is a non-sterilized, premenopausal female and agrees to abstain from heterosexual activity or to use an adequate method of contraception ( Note: Acceptable methods of birth control are: hormonal contraceptive, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, or vasectomy) - BMI ≥185 and ≤25 - Healthy as determined by: - Complete medical history, physical exam and - Standard 12-lead EKG - Complete blood count, blood chemistry , urinalysis with microscopy - Kidney USG - Participant understands the study procedures, and risks involved with the study and voluntarily agree to participate by giving informed written consent. Exclusion Criteria:• History of hypertension, diabetes (ADA guidelines), kidney disease o Participant has impaired renal function defined as glomerular filtration lower than 90 calculated by Cockcroft-Gault formula and 24 creatinine, also by urinary protein excretion > 200 mg/day or continuing active urinary sediment - History of myocardial infarction, cerebrovascular accident or transient ischemic attack - History of malignancy within last 5 years - Current febrile state - Participant is pregnant or nursing woman - Failure to give informed consent or comply with the protocol - Participant has received treatment with an investigational drug within the prior 3 months or is otherwise participating in another clinical trial |
परिणाम
प्राथमिक परिणाम उपाय
1. Evidence of the positive effect on natriuresis (level of sodium in urin sample) following the of GLP1 infusion [Within the 10 minutes after the infusion synthetic GLP-1 (1.5 pmol/kg/min) dissolved in 500 ml 0.9% saline]
