Clinical Trial Results:
The effect of lactate administration on cerebral blood flow during hypoglycemia
Summary
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EudraCT number |
2018-000684-82 |
Trial protocol |
NL |
Global end of trial date |
14 May 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Jun 2022
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First version publication date |
25 Jun 2022
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Other versions |
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Summary report(s) |
Paper Effect of lactate on CBF |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
2017-3968
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03730909 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Radboudumc
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Sponsor organisation address |
Geert Grooteplein Zuid 10, Nijmegen, Netherlands,
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Public contact |
clinical research centre nijmegen, Radboud umc, crcn@radboudumc.nl
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Scientific contact |
clinical research centre nijmegen, Radboud umc, crcn@radboudumc.nl
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 May 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 May 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
14 May 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To investigate the effect of intravenous lactate administration, compared to placebo, on thalamic (regional) CBF during euglycemia and hypoglycemia in patients with T1DM and normal awareness of hypoglycemia.
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Protection of trial subjects |
We did not use specific measures to protect trial subjects
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Background therapy |
- | ||
Evidence for comparator |
We used saline 0.9% infusion as a comparator. This is often used as a placebo to compare results to the test product. We can use the same amount of saline as the test product and it looks the same (from the outside) so it is suitable to use in a blinded study. | ||
Actual start date of recruitment |
11 Jun 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 9
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Worldwide total number of subjects |
9
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EEA total number of subjects |
9
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
9
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment of patients between 11th of June 2018 and 14th of May in 2019. | |||||||||
Pre-assignment
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Screening details |
Inclusion criteria: type 1 diabetes, age <50 years, BMI <30 kg/m2, and HbA1c levels not exceeding 9.0% (75 mmol/mol). Exclusion criteria: medication other than insulin, presence of any other medical condition, micro- and macrovascular complications of diabetes en contraindications for MRI. Three participants withdrawn, two were replaced. | |||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | |||||||||
Roles blinded |
Subject | |||||||||
Blinding implementation details |
We used bags to cover the sodium lactate and sodium chloride infusion fluids
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sodium lactate | |||||||||
Arm description |
Sodium lactate infusion day | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Sodium lactate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Sodium lactate 600 mmol/L
Sodium lactate infusion was started in a dose of 40 µmol/kg/min for 15 min, and then continued in a dose of 25 µmol/kg/min for
the remainder of the experiment
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Arm title
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Sodium chloride | |||||||||
Arm description |
Sodium chloride 0.9% infusion day | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Sodium chloride
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Sodium chloride 0.9% 500 mL, administered in an equivalent volume as compared to lactate infusion
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
Ten subjects were included, three withdrew consent, two of them were replaced and therefore the results of nine subjects were analysed. Mean age was 23.0±3.6 years, 4 male and 5 female subjects. Mean weight was 75.1±13.7 kg, and BMI 23.6±2.8 kg/m2. Median duration of diabetes was 7.0 (3.0–10.5) years. Mean HbA1c was 7.1±1.0 % (54.2±11.1 mmol/mol). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Sodium lactate
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Reporting group description |
Sodium lactate infusion day | ||
Reporting group title |
Sodium chloride
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Reporting group description |
Sodium chloride 0.9% infusion day |
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End point title |
Hypoglycemic symptom score | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
during hypoglycemia (45 minutes)
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Statistical analysis title |
T-test hypoglycemic symptom score | ||||||||||||
Comparison groups |
Sodium lactate v Sodium chloride
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Number of subjects included in analysis |
9
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
- | ||||||||||||
upper limit |
- | ||||||||||||
Variability estimate |
Standard error of the mean
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Notes [1] - Paired t-test for hypoglycemic symptoms during the two hypoglycemic glucose clamps |
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End point title |
Glucose infusion rates | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
during hypoglycemic glucose clamp
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Statistical analysis title |
T-test glucose infusion rate | ||||||||||||
Comparison groups |
Sodium lactate v Sodium chloride
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Number of subjects included in analysis |
9
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
- | ||||||||||||
upper limit |
- | ||||||||||||
Variability estimate |
Standard error of the mean
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Adverse events information
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Timeframe for reporting adverse events |
1 week after hypoglycemic clamp
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Assessment type |
Systematic | ||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
not used | ||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Limitations: sample size, difference in electrolyte concentration between sodium chloride and sodium lactate |