The Effect of Intravenous Lactate on Brain Lactate Concentrations During Hypoglycemia

September 14, 2017 updated by: Radboud University Medical Center

The Effect of Intravenous Lactate Administration on Brain Lactate Concentrations and pH During Euglycemia and Hypoglycemia in Patients With Type 1 Diabetes With and Without Impaired Awareness of Hypoglycemia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Lactate infusion
Subjects will receive an intravenous lactate infusion to elevate plasma lactate levels
Drug: Sodium Lactate
PLACEBO_COMPARATOR: NaCl infusion
As a control condition, subjects will receive intravenous NaCl infusion
Drug: SodiumChloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: during stable euglycemia (40 min) and hypoglycemia (45 min)
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
Time Frame: during stable euglycemia (40 min) and hypoglycemia (45 min)
during stable euglycemia (40 min) and hypoglycemia (45 min)

Secondary Outcome Measures

Outcome Measure
Time Frame
The changes in counterregulatory hormone and to hypoglycemia in response to lactate infusion, compared to placebo, in patients with normal awareness of hypoglycemia
Time Frame: during stable euglycemia (40 min) and hypoglycemia (45 min)
during stable euglycemia (40 min) and hypoglycemia (45 min)
The changes in and symptoms to hypoglycemia in response to lactate infusion, compared to placebo, in patients with normal awareness of hypoglycemia
Time Frame: during stable euglycemia (40 min) and hypoglycemia (45 min)
during stable euglycemia (40 min) and hypoglycemia (45 min)
The changes in brain pH in response to intravenous lactate administration, compared to placebo
Time Frame: during stable euglycemia (40 min) and hypoglycemia (45 min)
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
Time Frame: during stable euglycemia (40 min) and hypoglycemia (45 min)
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
Time Frame: during stable euglycemia (40 min) and hypoglycemia (45 min)
during stable euglycemia (40 min) and hypoglycemia (45 min)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

European Foundation for the Study of Diabetes
Dutch Diabetes Research Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2016

Primary Completion (ACTUAL)

May 1, 2017

Study Completion (ACTUAL)

August 1, 2017

Study Registration Dates

First Submitted

November 23, 2016

First Submitted That Met QC Criteria

September 14, 2017

First Posted (ACTUAL)

September 19, 2017

Study Record Updates

Last Update Posted (ACTUAL)

September 19, 2017

Last Update Submitted That Met QC Criteria

September 14, 2017

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Lac_iv

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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