Type1diabetesNCT03730909
The Effect Lactate Administration on Cerebral Blood Flow During Hypoglycemia
A study testing Sodium Lactate and Sodium chloride in people with Type1diabetes and Hypoglycemia Unawareness, run by Radboud University Medical Center at 1 site in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Type1diabetes, Hypoglycemia Unawareness
- What is being tested?
- Sodium Lactate and Sodium chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- 11 Jun 2018to 11 Jun 2019
- 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
- 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 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)
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Radoud university medical center
Nijmegen
Bastiaan de Galan, PhD
About this study
Official title: The Effect of Lactate Administration on Cerebral Blood Flow During Hypoglycemia; Are the Suppressive Effects of Lactate on Counterregulatory Responses to Hypoglycemia Reflected in an Altered CBF Response?
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.
Read more
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
- Being tested
- Sodium Lactate, Sodium chloride
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium LactateDrug
IV infusion
Sodium chlorideDrug
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Lactate infusion | Experimental | Subjects will receive an intravenous lactate infusion to elevate plasma lactate levels Receives: Drug: Sodium Lactate |
| NaCl infusion | Placebo comparator | As a control condition, subjects will receive intravenous NaCl infusion Receives: Drug: Sodium chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Secondary outcomes (4)
Global CBF in ml/100g/min measured with ASL-MRI
The change in global CBF in response to intravenous lactate infusion
Measured: during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Counterregulatory hormone responses to hypoglycemia
The difference in adrenaline (pmol/L) responses to hypoglycemia during lactate infusion compared to placebo
Measured: during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Symptom responses to hypoglycemia
The difference in symptom responses to hypoglycemia (meausured with a validated questionnaire) during lactate infusion compared to placebo
Measured: during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Measurements of metabolites in cell lysates or supernatants of the cultured immune cells
The effect of lactate administration on immune cell function and metabolism
Measured: during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2018
- Study start11 Jun 2018
- Primary completion11 Apr 2019 (estimated)
- Study completion11 Jun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type1diabetesStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03730909
- Sponsor's protocol ID
- Lactate_CBF
- Status last verified
- Oct 2018
- First submitted
- 22 Oct 2018
- Last updated
- 5 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 35321886
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Lactate Administration on Cerebral Blood Flow During Hypoglycemia; Are the Suppressive Effects of Lactate on Counterregulatory Responses to Hypoglycemia Reflected in an Altered CBF Response?
- ClinicalTrials.gov ID
- NCT03730909
- Acronym / sponsor ID
- Lactate_CBF
- Conditions
- Type1diabetes, Hypoglycemia Unawareness
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 11 Jun 2018 (actual)
- Primary completion
- 11 Apr 2019 (estimated)
- Study completion
- 11 Jun 2019 (estimated)
- First posted
- 5 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lactate infusion | Experimental | Drug: Sodium LactateSubjects will receive an intravenous lactate infusion to elevate plasma lactate levels |
| NaCl infusion | Placebo comparator | Drug: Sodium chlorideAs a control condition, subjects will receive intravenous NaCl infusion |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium LactateIV infusion | Drug | Lactate infusion |
| Sodium chlorideIV infusion | Drug | NaCl infusion |
Primary outcome
Regional CBF in ml/100g/min measured with ASL-MRI
Time frame: during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
The change in regional thalamic CBF in response to intravenous lactate infusion compared to placebo, during hypoglycemia
4 secondary outcomes
Global CBF in ml/100g/min measured with ASL-MRI
Time frame: during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Counterregulatory hormone responses to hypoglycemia
Time frame: during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Symptom responses to hypoglycemia
Time frame: during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Measurements of metabolites in cell lysates or supernatants of the cultured immune cells
Time frame: during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2018.
- Derived from this study: PubMed 35321886van 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sodium Lactate and Sodium chloride in people with Type1diabetes and Hypoglycemia Unawareness, 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: status not confirmed, as of the sponsor's last update on 5 Nov 2018. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bastiaan de Galan, PhD (0243613286, bastiaan.degalan@radboud.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Regional CBF in ml/100g/min measured with ASL-MRI (time frame: during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)). 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 NCT03730909, which also lists 1 linked publication.
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 5 Nov 2018.