The Effect Lactate Administration on Cerebral Blood Flow During Hypoglycemia
Primary Purpose
Type1diabetes, Hypoglycemia Unawareness
Status
Unknown status
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Sodium Lactate
Sodium chloride
Sponsored by
About this trial
This is an interventional basic science trial for Type1diabetes
Eligibility Criteria
Inclusion Criteria:
- Diabetes duration ≥ 1 year
- Age: 18-50 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
Exclusion Criteria:
- Inability to provide informed consent
- Use medication other than insulin, except for oral contraceptives or stable thyroxin supplementation therapy
- Presence of any other medical condition that might interfere with the study protocol, such as brain injuries, epilepsy, a major cardiovascular disease event or cardiac failure, known liver disease, anxiety disorders or a history of panic attacks.
- Microvascular complications of T1DM: Proliferative retinopathy, symptomatic diabetic neuropathy (including autonomic neuropathy) or Nephropathy; clinical/overt albuminuria or an estimated glomerular filtration rate <60ml/min/1.73m2.
- MRI contraindications (pregnancy, severe claustrophobia, metal parts in body)
Sites / Locations
- Radoud university medical centerRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Lactate infusion
NaCl infusion
Arm Description
Subjects will receive an intravenous lactate infusion to elevate plasma lactate levels
As a control condition, subjects will receive intravenous NaCl infusion
Outcomes
Primary Outcome Measures
Regional CBF in ml/100g/min measured with ASL-MRI
The change in regional thalamic CBF in response to intravenous lactate infusion compared to placebo, during hypoglycemia
Secondary Outcome Measures
Global CBF in ml/100g/min measured with ASL-MRI
The change in global CBF in response to intravenous lactate infusion
Counterregulatory hormone responses to hypoglycemia
The difference in adrenaline (pmol/L) responses to hypoglycemia during lactate infusion compared to placebo
Symptom responses to hypoglycemia
The difference in symptom responses to hypoglycemia (meausured with a validated questionnaire) during lactate infusion compared to placebo
Measurements of metabolites in cell lysates or supernatants of the cultured immune cells
The effect of lactate administration on immune cell function and metabolism
Full Information
NCT ID
NCT03730909
First Posted
October 22, 2018
Last Updated
November 1, 2018
Sponsor
Radboud University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03730909
Brief Title
The Effect Lactate Administration on Cerebral Blood Flow During Hypoglycemia
Official Title
The Effect of Lactate Administration on Cerebral Blood Flow During Hypoglycemia; Are the Suppressive Effects of Lactate on Counterregulatory Responses to Hypoglycemia Reflected in an Altered CBF Response?
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Unknown status
Study Start Date
June 11, 2018 (Actual)
Primary Completion Date
April 11, 2019 (Anticipated)
Study Completion Date
June 11, 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
It is thought that altered brain lactate handling is involved in the development of impaired awareness of hypoglycemia (IAH), i.e. the inability to timely detect hypoglycemia in people with type 1 diabetes (T1DM). Infusion of lactate diminishes symptomatic and hormonal responses to hypoglycemia in patients with normal awareness of hypoglycemia (NAH), resembling the situation of patients with IAH. It is unknown whether this attenuating effect is due to brain lactate oxidation or the result of lactate-induced alterations of global and regional cerebral blood flow (CBF).
Normally, hypoglycemia causes a redistribution of CBF towards the thalamus, from where the sympathetic response to hypoglycemia is coordinated, but in IAH this effect is absent and global CBF is increased. We hypothesize that lactate infusion in patients with NAH will result in blunting of thalamic activation and/or enhanced global CBF. If so, these results may help delineating the pathogenesis of IAH which eventually creates new avenues to protect against the morbidity associated with hypoglycemia and IAH.
Study design: Single-blind placebo controlled, randomized cross-over intervention study Study population: T1DM patients with NAH (n=10) Intervention: On two separate occasions, patients with T1DM and NAH will undergo a hyperinsulinemic euglycemic-hypoglycemic glucose clamp with or without the infusion of exogenous lactate. ASL-MRI will be applied to measure global and regional changes in CBF.
Main study parameters/endpoints: The change in regional thalamic CBF in response to intravenous lactate infusion compared to placebo, during hypoglycemia
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type1diabetes, Hypoglycemia Unawareness
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lactate infusion
Arm Type
Experimental
Arm Description
Subjects will receive an intravenous lactate infusion to elevate plasma lactate levels
Arm Title
NaCl infusion
Arm Type
Placebo Comparator
Arm Description
As a control condition, subjects will receive intravenous NaCl infusion
Intervention Type
Drug
Intervention Name(s)
Sodium Lactate
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
Sodium chloride
Intervention Description
IV infusion
Primary Outcome Measure Information:
Title
Regional CBF in ml/100g/min measured with ASL-MRI
Description
The change in regional thalamic CBF in response to intravenous lactate infusion compared to placebo, during hypoglycemia
Time Frame
during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Secondary Outcome Measure Information:
Title
Global CBF in ml/100g/min measured with ASL-MRI
Description
The change in global CBF in response to intravenous lactate infusion
Time Frame
during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Title
Counterregulatory hormone responses to hypoglycemia
Description
The difference in adrenaline (pmol/L) responses to hypoglycemia during lactate infusion compared to placebo
Time Frame
during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Title
Symptom responses to hypoglycemia
Description
The difference in symptom responses to hypoglycemia (meausured with a validated questionnaire) during lactate infusion compared to placebo
Time Frame
during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Title
Measurements of metabolites in cell lysates or supernatants of the cultured immune cells
Description
The effect of lactate administration on immune cell function and metabolism
Time Frame
during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diabetes duration ≥ 1 year
Age: 18-50 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
Exclusion Criteria:
Inability to provide informed consent
Use medication other than insulin, except for oral contraceptives or stable thyroxin supplementation therapy
Presence of any other medical condition that might interfere with the study protocol, such as brain injuries, epilepsy, a major cardiovascular disease event or cardiac failure, known liver disease, anxiety disorders or a history of panic attacks.
Microvascular complications of T1DM: Proliferative retinopathy, symptomatic diabetic neuropathy (including autonomic neuropathy) or Nephropathy; clinical/overt albuminuria or an estimated glomerular filtration rate <60ml/min/1.73m2.
MRI contraindications (pregnancy, severe claustrophobia, metal parts in body)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bastiaan de Galan, PhD
Phone
0243613286
Email
bastiaan.degalan@radboud.nl
Facility Information:
Facility Name
Radoud university medical center
City
Nijmegen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bastiaan de Galan, PhD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35321886
Citation
van Meijel LA, van Asten JJA, Grandjean J, Heerschap A, Tack CJ, van der Graaf M, Wiegers EC, de Galan BE. Effect of lactate administration on cerebral blood flow during hypoglycemia in people with type 1 diabetes. BMJ Open Diabetes Res Care. 2022 Mar;10(2):e002401. doi: 10.1136/bmjdrc-2021-002401.
Results Reference
derived
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The Effect Lactate Administration on Cerebral Blood Flow During Hypoglycemia
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