The Role of IntraNasal Insulin in Regulating HepaTic Lipid COntent in HUMANS (INTO_humans)
The Role of IntraNasal Insulin in Regulating HepaTic Lipid COntent in HUMANS a Randomized, Controlled, Double Blinded Trial
Non-alcoholic fatty liver disease (NAFLD) is a common human liver pathology, closely associated with the obesity pandemic and insulin resistance. In the insulin resistant state the liver remains sensitive to pro-lipogenic signals of insulin, which further promote lipid accumulation. Secretion of very-low-density-lipoproteins (VLDL), the main carriers of triglycerides (TG) in the plasma, is the principal pathway for the liver to mobilize and dispose of lipids. Thus, hepatic TG export must not be too low in order to prevent steatosis. Our preliminary data from animal experiments suggest that enhanced brain insulin signaling promotes hepatic VLDL secretion, and reduces lipid accumulation in the liver. It remains to be tested whether other insulin sensitive tissues, such as the myocardium or the skeletal muscle, are also affected. In humans, neuropeptides, including insulin, can be delivered to the brain via an intranasal (IN) route of administration, without causing relevant systemic side effects.
Therefore, we hypothesize that by enhancing brain insulin signaling using chronic IN insulin administration hepatic TG export increases and prohibits lipid accumulation in the liver and other insulin sensitive tissues, such as the myocardium and the skeletal muscle.
연구 개요
상태
정황
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
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Vienna, 오스트리아, 1090
- Medical University of Vienna, Department of Internal Medicine III
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- BMI 22 - 27 kg/m2
- Age between 18 - 65 years
- Male sex
Exclusion Criteria:
- smoking
- regular medication
- metabolic or liver illnesses
- tendency towards claustrophobia
- Chronic sinusitis, diagnosed nasal polyposis, diagnosed severe septum deviation
- metal devices or other magnetic material in or on the subjects body which will be hazardous for NMR investigation [heart pacemaker, brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, post coronary by-pass graft (epicardial pace wires), penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt-spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips), embolization coil, or any metal fragments or shrapnel in the body].
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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위약 비교기: Insulin dilution buffer
During a subsequent 4-week treatment phase subjects will be randomly assigned to receive intranasal insulin (40 IE) Actrapid (100IE/mL); two 0.1 ml puffs per nostril) or placebo (insulin dilution buffer Novo Nordisk; two 0.1 ml puffs per nostril) four times a day (in total 160 IE Actrapid per day) before each main meal and before going to bed. 40 IE IN insulin enhances insulin concentration in the CSF without any changes in systemic insulin and glucose concentration, and no risk for hypoglycemia. Ectopic lipid content and heart function will be assessed weekly by non-invasive 1H magnetic resonance spectroscopy. |
intranasal insulin (40 IE) Actrapid (100IE/mL); two 0.1 ml puffs per nostril) or placebo (insulin dilution buffer Novo Nordisk; two 0.1 ml puffs per nostril) four times a day (in total 160 IE Actrapid per day) before each main meal and before going to bed.
40 IE IN insulin enhances insulin concentration in the CSF without any changes in systemic insulin and glucose concentration, and no risk for hypoglycemia
다른 이름들:
1H MR spectroscopy and imaging will be performed on the on on the 3.0-T Tim Trio System (Siemens Erlangen Germany).
MR Spectroscopy and imaging measurements will last no more than 90 minutes all together.
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활성 비교기: Intranasal Insulin administration
During a subsequent 4-week treatment phase subjects will be randomly assigned to receive intranasal insulin (40 IE) Actrapid (100IE/mL); two 0.1 ml puffs per nostril) or placebo (insulin dilution buffer Novo Nordisk; two 0.1 ml puffs per nostril) four times a day (in total 160 IE Actrapid per day) before each main meal and before going to bed. 40 IE IN insulin enhances insulin concentration in the CSF without any changes in systemic insulin and glucose concentration, and no risk for hypoglycemia. Ectopic lipid content and heart function will be assessed weekly by non-invasive 1H magnetic resonance spectroscopy. |
1H MR spectroscopy and imaging will be performed on the on on the 3.0-T Tim Trio System (Siemens Erlangen Germany).
MR Spectroscopy and imaging measurements will last no more than 90 minutes all together.
intranasal insulin (40 IE) Actrapid (100IE/mL); two 0.1 ml puffs per nostril) or placebo (insulin dilution buffer Novo Nordisk; two 0.1 ml puffs per nostril) four times a day (in total 160 IE Actrapid per day) before each main meal and before going to bed.
40 IE IN insulin enhances insulin concentration in the CSF without any changes in systemic insulin and glucose concentration, and no risk for hypoglycemia
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Changes in total lipid content in the liver
기간: one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
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1H magnetic resonance spectroscopy
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one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Changes of hepatic Lipid composition
기간: one week before & baseline & 1,2,3 and 4 weeks after intranasal insulin administration
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1H magnetic resonance spectroscopy
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one week before & baseline & 1,2,3 and 4 weeks after intranasal insulin administration
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Changes of myocardial lipid content
기간: baseline, 2 and 4 weeks after intranasal insulin administration
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1H magnetic resonance spectroscopy
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baseline, 2 and 4 weeks after intranasal insulin administration
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Changes of myocardial lipid composition
기간: baseline, 2 and 4 weeks after intranasal insulin administration
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1H magnetic resonance spectroscopy
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baseline, 2 and 4 weeks after intranasal insulin administration
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Changes of skeletal muscle lipid content
기간: baseline, 2 and 4 weeks after intranasal insulin administration
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1H magnetic resonance spectroscopy
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baseline, 2 and 4 weeks after intranasal insulin administration
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Changes of lipid composition in skeletal muscle
기간: baseline, 2 and 4 weeks after intranasal insulin administration
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1H magnetic resonance spectroscopy
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baseline, 2 and 4 weeks after intranasal insulin administration
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changes in heart function
기간: baseline, 2 and 4 weeks after intranasal insulin administration
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magnetic resonance imaging
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baseline, 2 and 4 weeks after intranasal insulin administration
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Changes of parameters of glucose and lipid metabolism
기간: one week before & baseline & 1,2,3 and 4 weeks after initiation of intranasal insulin administration
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fasting Glucose, HbA1c, Cholesterol, LDL, HDL, TGs, non-HDL Cholesterol, FFAs
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one week before & baseline & 1,2,3 and 4 weeks after initiation of intranasal insulin administration
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Lipid composition in plasma
기간: one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
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one week before & at baseline & 1,2,3 and 4 weeks after intranasal insulin administration
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공동 작업자 및 조사자
수사관
- 수석 연구원: Michael Krebs, MD, Prof., Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (예상)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- INTO_humans
- 2013-004463-32 (EudraCT 번호)
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
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