The Effect Lactate Administration on Cerebral Blood Flow During Hypoglycemia

NCT ID: NCT03730909

Last Updated: 2018-11-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-11
• Study Completion Date: 2019-06-11

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

Conditions

Type1diabetes; Hypoglycemia Unawareness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Lactate infusion

Subjects will receive an intravenous lactate infusion to elevate plasma lactate levels

Group Type: EXPERIMENTAL

Sodium Lactate

Intervention Type: DRUG

IV infusion

NaCl infusion

As a control condition, subjects will receive intravenous NaCl infusion

Group Type: PLACEBO_COMPARATOR

Sodium chloride

Intervention Type: DRUG

IV infusion

Interventions

Sodium Lactate

IV infusion

Intervention Type: DRUG

Sodium chloride

IV infusion

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Radoud university medical center

Nijmegen, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Bastiaan de Galan, PhD

Role: CONTACT

bastiaan.degalan@radboud.nl

0243613286

Facility Contacts

Bastiaan de Galan, PhD

Role: primary

References

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.

Reference Type: DERIVED

PMID: 35321886 (View on PubMed)

Other Identifiers

Lactate_CBF

Identifier Type: -

Identifier Source: org_study_id