The Effect of Intravenous Lactate on Brain Lactate Concentrations During Hypoglycemia

Not Applicable

Completed

• Conditions: Type 1 Diabetes Mellitus With Hypoglycemia
• Interventions: Drug: SodiumChloride; Drug: Sodium Lactate

• Registration Number: NCT03286816
• Lead Sponsor: Radboud University Medical Center

Brief Summary

Patients with type 1 diabetes (T1DM) who are unable to perceive symptoms of hypoglycemia, referred to as impaired awareness of hypoglycemia (IAH), are at very high risk of severe hypoglycemia. IAH affects approximately 25% of patients with T1DM. Brain lactate may be involved in the development of IAH. A recent study indicated increased brain lactate utilization during hypoglycemia in T1DM patients with IAH, which did not occur in patients with normal awareness of hypoglycemia (NAH). Conversely, administration of lactate to patients with NAH has been shown to attenuate counterregulatory hormone responses to and symptomatic awareness of hypoglycemia, thus causing a situation that resembles IAH. It has, however, not been demonstrated whether the excess of lactate is actually taken up or metabolized by the brain, and if so whether this occurs under euglycemic or hypoglycemic conditions or both.

This project consists of two related studies. The objective of part 1 is to investigate the effect of elevated plasma lactate levels that are sufficient to impair awareness of hypoglycemia on brain lactate concentrations during euglycemia and hypoglycemia in T1DM patients with NAH. The objective of part 2 is to compare the effect of exogenous lactate on brain lactate concentrations between T1DM patients with NAH and T1DM patients with IAH.

Furthermore, this study aims to determine the effect of acute hypoglycemia on the inflammatory function and composition of peripheral blood mononuclear cells.

Detailed Description

Not available

Study Timeline

• Status Verified: 2016-11
• Study Start: 2016-11
• Study First Submitted: 2016-11-23
• Primary Completion: 2017-05
• Study Completion: 2017-08
• Study First Submitted QC: 2017-09-14
• Last Update Submitted: 2017-09-14
• Study First Posted: 2017-09-19
• Last Update Posted: 2017-09-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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 or >=3
• 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, known liver disease, anxiety disorders or a history of panic attacks.
• Microvascular complications of T1DM: Proliferative retinopathy, Symptomatic diabetic neuropathy (including autonomic neuropathy), Nephropathy; clinical/overt albuminuria or an estimated glomerular filtration rate <60ml/min/1.73m2
• MR(I) contraindications (pregnancy, severe claustrophobia, metal parts in body)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
NaCl infusion	SodiumChloride	As a control condition, subjects will receive intravenous NaCl infusion
Lactate infusion	Sodium Lactate	Subjects will receive an intravenous lactate infusion to elevate plasma lactate levels

Primary Outcome Measures

Name	Time	Method
the effect of intravenous lactate administration, compared to placebo, on brain lactate concentrations during euglycemia and hypoglycemia in patients with T1DM and normal awareness of hypoglycemia	during stable euglycemia (40 min) and hypoglycemia (45 min)
the effect of exogenous lactate on brain lactate concentrations during euglycemia and hypoglycemia between T1DM patients with normal awareness of hypoglycemia and T1DM patients with impaired awareness of hypoglycemia	during stable euglycemia (40 min) and hypoglycemia (45 min)

Secondary Outcome Measures

Name	Time	Method
The changes in and symptoms to hypoglycemia in response to lactate infusion, compared to placebo, in patients with normal awareness of hypoglycemia	during stable euglycemia (40 min) and hypoglycemia (45 min)
The changes in brain pH in response to intravenous lactate administration, compared to placebo	during stable euglycemia (40 min) and hypoglycemia (45 min)
Changes in immune cell composition capacity in response to hypoglycemia compared to euglycemia and in response to lactate infusion compared to placebo	during stable euglycemia (40 min) and hypoglycemia (45 min)
The changes in counterregulatory hormone and to hypoglycemia in response to lactate infusion, compared to placebo, in patients with normal awareness of hypoglycemia	during stable euglycemia (40 min) and hypoglycemia (45 min)
Changes in immune cell cytokine production capacity in response to hypoglycemia compared to euglycemia and in response to lactate infusion compared to placebo	during stable euglycemia (40 min) and hypoglycemia (45 min)

Trial Locations

Locations (1)

Radboud umc; 🇳🇱 Nijmegen, Netherlands