The Effect Lactate Administration on Cerebral Blood Flow During Hypoglycemia

NCT03730909 | Unknown

• 1 other identifier: Lactate_CBF
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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

  during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)

Secondary Outcomes (4)

• Global CBF in ml/100g/min measured with ASL-MRI

  during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)

• Counterregulatory hormone responses to hypoglycemia

  during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)

• Symptom responses to hypoglycemia

  during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)

• Measurements of metabolites in cell lysates or supernatants of the cultured immune cells

  during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)

Study Arms (2)

Lactate infusion

EXPERIMENTAL

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

Drug: Sodium Lactate

NaCl infusion

PLACEBO COMPARATOR

As a control condition, subjects will receive intravenous NaCl infusion

Drug: Sodium chloride

Interventions

Sodium Lactate DRUG

IV infusion

Lactate infusion

Sodium chloride DRUG

IV infusion

NaCl infusion

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radoud university medical center

Nijmegen, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 35321886 DERIVED

MeSH Terms

Interventions

Sodium Lactate; Sodium Chloride

Intervention Hierarchy (Ancestors)

Lactates; Hydroxy Acids; Carboxylic Acids; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Bastiaan de Galan, PhD

CONTACT

0243613286; bastiaan.degalan@radboud.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2018
• First Posted: November 5, 2018
• Study Start: June 11, 2018
• Primary Completion: April 11, 2019
• Study Completion: June 11, 2019
• Last Updated: November 5, 2018

Record last verified: 2018-10

Locations

NL (1)