- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT02308293
The Role of Endogenous Lactate in Brain Preservation and Counterregulatory Defenses Against Hypoglycemia
The Effect of Exercise-induced Hyperlacticacidemia on Counterregulatory Responses, Symptoms, Cognitive Function and Brain Lactate Accumulation During Hypoglycemia in (Hypoglycemic Unaware)Type I Diabetes Patients and Normal Controls
Iatrogenic hypoglycemia is the most frequent acute complication of insulin therapy in people with type 1 diabetes (T1DM). Recurrent hypoglycemic events initiate a process of habituation, characterized by suppression of hypoglycemic symptoms, eventually leading to hypoglycemia unawareness, which creates a particularly high risk of severe hypoglycemia. Recent evidence suggest a pivotal role for (brain) lactate in the pathogenesis of hypoglycemia unawareness. Indeed, exogenous lactate administration may preserve brain function and attenuate counterregulatory responses to and symptomatic awareness of hypoglycemia. It is unknown whether endogenous elevation of plasma lactate produces the same effects and whether such effects differ between patients with T1DM with and without hypoglycemia unawareness and healthy controls.
Objective: To investigate the effect of elevated levels of endogenous lactate on brain lactate accumulation and on counterregulatory responses to, symptomatic awareness of and cognitive function during hypoglycemia in patients with T1DM with and without hypoglycemia unawareness and normal controls.
Hypothesis: The investigators hypothesize first that endogenous lactate, when raised through high intensity exercise, preserves neuronal metabolism during subsequent hypoglycemia, which in turn will attenuate counterregulatory hormone responses, appearance of symptoms and deterioration of cognitive function. Second, the investigators posit that these effects will be augmented in patients with hypoglycemia unawareness compared to healthy subjects and T1DM patients with normal awareness as a consequence of greater transport capacity of lactate into the brain.
연구 개요
연구 유형
등록 (실제)
단계
- 해당 없음
연락처 및 위치
연구 장소
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Nijmegen, 네덜란드
- Radboud UMC
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion criteria for healthy subjects
- Age: 18-40 years
- Body-Mass Index: 18-30 kg/m2
- Blood pressure: <160/90 mmHg
- Recreationally active: i.e. taking part in competitive sport or regular exercise training, of a non-professional nature, once or more a week.
Inclusion criteria T1DM patients with normal hypoglycemic awareness
- Diabetes duration ≥ 1 year
- Age: 18-40 years
- Body-Mass Index: 18-30 kg/m2
- HbA1c: 42-75 mmol/mol (6-9%)
- Outcome Clarke questionnaire: 0-1
- Blood pressure: <160/90 mmHg
- Recreationally active: i.e. taking part in competitive sport or regular exercise training, of a non-professional nature, once or more a week
Inclusion criteria T1DM patients with hypoglycemia unawareness
- Diabetes duration ≥ 1 year
- Age: 18-40 years
- Body-Mass Index: 18-30 kg/m2
- HbA1c: 42-75 mmol/mol (6-9%)
- Outcome Clarke questionnaire: =>3
- Blood pressure: <160/90 mmHg
- Recreationally active
Exclusion criteria:
- Inability to provide informed consent
- Presence of any medical condition that might interfere with the study protocol, such as brain injuries, epilepsy, a major cardiovascular disease event or anxiety disorders
- Use of any medication, except for oral contraceptives
- MR(I) contraindications (pregnancy, severe claustrophobia, metal parts in body)
- Orthopedic and/or neurological diseases that impair exercise
- Cardiopulmonary disease as stated in the 2001 American heart association and 2002 American college of cardiology/American heart association guidelines
Additional exclusion criteria for all T1DM patients:
- Use of any other medication than insulin, except for oral contraceptives or stable thyroxine supplementation therapy
- complications of T1DM, including proliferative retinopathy, neuropathy or nephropathy
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 무작위
- 중재 모델: 크로스오버 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
---|---|
실험적: High intensity exercise
Subjects will preform a high intensity training exercise (3* 30 seconds all out sprint on a cycle ergometer) to raise plasma lactate levels
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3x30 seconds 'all out' sprints
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가짜 비교기: Lay down comfortably
As a control conditions, subjects wil lay down comfortably and rest
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rest
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
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Plasma level of adrenaline in response to hypoglycemia (Adrenaline, measured in arterial plasma)
기간: during 60 m of hypoglycemia
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during 60 m of hypoglycemia
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Plasma levels of other counter-regulatory hormones (Levels of counter-regulatory hormones measured in arterial plasma)
기간: During 60 min hypoglycemia
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Levels of counter-regulatory hormones measured in arterial plasma
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During 60 min hypoglycemia
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Glucose infusion rate (Amount of glucose 20% necessary to maintain plasma glucose at steady state values)
기간: During 60 min hypoglycemia
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Amount of glucose 20% necessary to maintain plasma glucose at steady state values
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During 60 min hypoglycemia
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Plasma lactate levels (Lactate levels measured in arterial plasma)
기간: During 60 min hypoglycemia
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Lactate levels measured in arterial plasma
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During 60 min hypoglycemia
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Cognitive functioning, as measured by cognitive tests
기간: During 60 min hypoglycemia
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Cognitive test will be: Dutch State Trait Anxiety Inventory, Digit Span, Stroop color word test, word fluency test, trail making test and Pasat
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During 60 min hypoglycemia
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Plasma levels of inflammatory markers (levels of cytokines)
기간: During 60 min hypoglycemia
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levels of cytokines
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During 60 min hypoglycemia
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Brain perfusion measured with ASL-MRI
기간: During 60 min hypoglycemia
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Brain perfusion measured with ASL-MRI
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During 60 min hypoglycemia
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Brain lactate accumulation measured with 1H-MRS
기간: During 60 min of hypoglycemia
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Brain lactate levels measured with 1H-MRS
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During 60 min of hypoglycemia
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Plasma glucose concentration
기간: During 60 min hypoglycemia
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Plasma glucose concentration, necessary to adjust glucose infusion rate
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During 60 min hypoglycemia
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Plasma insulin concentration (Insulin levels, measured in arterial plasma)
기간: During 60 min hypoglycemia
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Insulin levels, measured in arterial plasma
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During 60 min hypoglycemia
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공동 작업자 및 조사자
수사관
- 수석 연구원: Bastiaan de Galan, Dr., Radboud University Medical Center
간행물 및 유용한 링크
일반 간행물
- van de Ven KC, van der Graaf M, Tack CJ, Klomp DW, Heerschap A, de Galan BE. Optimized [1-(13)C]glucose infusion protocol for 13C magnetic resonance spectroscopy at 3T of human brain glucose metabolism under euglycemic and hypoglycemic conditions. J Neurosci Methods. 2010 Jan 30;186(1):68-71. doi: 10.1016/j.jneumeth.2009.10.025. Epub 2009 Nov 11.
- van de Ven KC, de Galan BE, van der Graaf M, Shestov AA, Henry PG, Tack CJ, Heerschap A. Effect of acute hypoglycemia on human cerebral glucose metabolism measured by (1)(3)C magnetic resonance spectroscopy. Diabetes. 2011 May;60(5):1467-73. doi: 10.2337/db10-1592. Epub 2011 Apr 4.
- van de Ven KC, van der Graaf M, Tack CJ, Heerschap A, de Galan BE. Steady-state brain glucose concentrations during hypoglycemia in healthy humans and patients with type 1 diabetes. Diabetes. 2012 Aug;61(8):1974-7. doi: 10.2337/db11-1778. Epub 2012 Jun 11.
- De Feyter HM, Mason GF, Shulman GI, Rothman DL, Petersen KF. Increased brain lactate concentrations without increased lactate oxidation during hypoglycemia in type 1 diabetic individuals. Diabetes. 2013 Sep;62(9):3075-80. doi: 10.2337/db13-0313. Epub 2013 May 28.
- Wiegers EC, Rooijackers HM, van Asten JJA, Tack CJ, Heerschap A, de Galan BE, van der Graaf M. Elevated brain glutamate levels in type 1 diabetes: correlations with glycaemic control and age of disease onset but not with hypoglycaemia awareness status. Diabetologia. 2019 Jun;62(6):1065-1073. doi: 10.1007/s00125-019-4862-9. Epub 2019 Apr 19.
- Maddock RJ, Casazza GA, Buonocore MH, Tanase C. Vigorous exercise increases brain lactate and Glx (glutamate+glutamine): a dynamic 1H-MRS study. Neuroimage. 2011 Aug 15;57(4):1324-30. doi: 10.1016/j.neuroimage.2011.05.048. Epub 2011 May 27.
- Wiegers EC, Rooijackers HM, Tack CJ, Groenewoud HJMM, Heerschap A, de Galan BE, van der Graaf M. Effect of Exercise-Induced Lactate Elevation on Brain Lactate Levels During Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia. Diabetes. 2017 Dec;66(12):3105-3110. doi: 10.2337/db17-0794. Epub 2017 Sep 21.
- Rooijackers HM, Wiegers EC, van der Graaf M, Thijssen DH, Kessels RPC, Tack CJ, de Galan BE. A Single Bout of High-Intensity Interval Training Reduces Awareness of Subsequent Hypoglycemia in Patients With Type 1 Diabetes. Diabetes. 2017 Jul;66(7):1990-1998. doi: 10.2337/db16-1535. Epub 2017 Apr 18.
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
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 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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