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The Effect of Intravenous Lactate on Brain Lactate Concentrations During Hypoglycemia

NCT ID: NCT03286816

Last Updated: 2017-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-30

Study Completion Date

2017-08-31

Brief Summary

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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

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Conditions

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Type 1 Diabetes Mellitus With Hypoglycemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants

Study Groups

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Lactate infusion

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

Group Type EXPERIMENTAL

Sodium Lactate

Intervention Type DRUG

NaCl infusion

As a control condition, subjects will receive intravenous NaCl infusion

Group Type PLACEBO_COMPARATOR

SodiumChloride

Intervention Type DRUG

Interventions

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SodiumChloride

Intervention Type DRUG

Sodium Lactate

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dutch Diabetes Research Foundation

OTHER

Sponsor Role collaborator

European Foundation for the Study of Diabetes

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Radboud umc

Nijmegen, , Netherlands

Site Status

Countries

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Netherlands

References

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De Feyter HM, Mason GF, Shulman GI, Rothman DL, Petersen KF. Increased brain lactate concentrations without increased lactate oxidation during hypoglycemia in type 1 diabetic individuals. Diabetes. 2013 Sep;62(9):3075-80. doi: 10.2337/db13-0313. Epub 2013 May 28.

Reference Type BACKGROUND
PMID: 23715622 (View on PubMed)

Veneman T, Mitrakou A, Mokan M, Cryer P, Gerich J. Effect of hyperketonemia and hyperlacticacidemia on symptoms, cognitive dysfunction, and counterregulatory hormone responses during hypoglycemia in normal humans. Diabetes. 1994 Nov;43(11):1311-7. doi: 10.2337/diab.43.11.1311.

Reference Type BACKGROUND
PMID: 7926305 (View on PubMed)

Maran A, Crepaldi C, Trupiani S, Lucca T, Jori E, Macdonald IA, Tiengo A, Avogaro A, Del Prato S. Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and type I diabetic subjects. Diabetologia. 2000 Jun;43(6):733-41. doi: 10.1007/s001250051371.

Reference Type BACKGROUND
PMID: 10907119 (View on PubMed)

Wiegers EC, Rooijackers HM, Tack CJ, Heerschap A, de Galan BE, van der Graaf M. Brain Lactate Concentration Falls in Response to Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia. Diabetes. 2016 Jun;65(6):1601-5. doi: 10.2337/db16-0068. Epub 2016 Mar 18.

Reference Type BACKGROUND
PMID: 26993070 (View on PubMed)

Wiegers EC, Rooijackers HM, van Asten JJA, Tack CJ, Heerschap A, de Galan BE, van der Graaf M. Elevated brain glutamate levels in type 1 diabetes: correlations with glycaemic control and age of disease onset but not with hypoglycaemia awareness status. Diabetologia. 2019 Jun;62(6):1065-1073. doi: 10.1007/s00125-019-4862-9. Epub 2019 Apr 19.

Reference Type DERIVED
PMID: 31001674 (View on PubMed)

Other Identifiers

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Lac_iv

Identifier Type: -

Identifier Source: org_study_id