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Type 1 Diabetes Mellitus With HypoglycemiaNCT03286816

The Effect of Intravenous Lactate on Brain Lactate Concentrations During Hypoglycemia

A study testing SodiumChloride and Sodium Lactate in people with Type 1 Diabetes Mellitus With Hypoglycemia, run by Radboud University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 years
What is being tested?
SodiumChloride and Sodium Lactate
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
19 participants
Where
1 siteNetherlands
Study dates
Nov 2016to Aug 2017
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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)

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Radboud umc

    Nijmegen

Other trials in Netherlands

About this study

Official title: 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.

Being tested
SodiumChloride, Sodium Lactate
Keywords
type 1 diabetes mellitus, impaired awareness of hypoglycemia, lactate, MR spectroscopy
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SodiumChlorideDrug

  • Sodium LactateDrug

Study groups in NCT03286816
Study groupRoleWhat they receive
Lactate infusionExperimentalSubjects will receive an intravenous lactate infusion to elevate plasma lactate levels
Receives: Drug: Sodium Lactate
NaCl infusionPlacebo comparatorAs a control condition, subjects will receive intravenous NaCl infusion
Receives: Drug: SodiumChloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: during stable euglycemia (40 min) and hypoglycemia (45 min)

  2. 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

    Measured: during stable euglycemia (40 min) and hypoglycemia (45 min)

Secondary outcomes (5)

  1. The changes in counterregulatory hormone and to hypoglycemia in response to lactate infusion, compared to placebo, in patients with normal awareness of hypoglycemia

    Measured: during stable euglycemia (40 min) and hypoglycemia (45 min)

  2. The changes in and symptoms to hypoglycemia in response to lactate infusion, compared to placebo, in patients with normal awareness of hypoglycemia

    Measured: during stable euglycemia (40 min) and hypoglycemia (45 min)

  3. The changes in brain pH in response to intravenous lactate administration, compared to placebo

    Measured: during stable euglycemia (40 min) and hypoglycemia (45 min)

  4. Changes in immune cell composition capacity in response to hypoglycemia compared to euglycemia and in response to lactate infusion compared to placebo

    Measured: during stable euglycemia (40 min) and hypoglycemia (45 min)

  5. Changes in immune cell cytokine production capacity in response to hypoglycemia compared to euglycemia and in response to lactate infusion compared to placebo

    Measured: during stable euglycemia (40 min) and hypoglycemia (45 min)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2017
  2. Study startNov 2016
  3. Primary completionMay 2017
  4. Study completionAug 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03286816
Sponsor's protocol ID
Lac_iv
Status last verified
Nov 2016
First submitted
23 Nov 2016
Last updated
19 Sep 2017
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 23715622

  • 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.

    PubMed 7926305

  • 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.

    PubMed 10907119

  • 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.

    PubMed 26993070

  • 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.

    PubMed 31001674

Questions about this trial

What is this clinical trial studying?

A study testing SodiumChloride and Sodium Lactate in people with Type 1 Diabetes Mellitus With Hypoglycemia, run by Radboud University Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03286816, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2017.

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