Type 2 Diabetes
Conditions
Brief summary
There is evidence that inhibition of FFA-release by acipimox is associated with a significant decrease in myocardial lipid content (MYCL) as well as the ejection fraction (as a marker of systolic left ventricular function) in healthy subjects, indicating, that the heart is dependent on a constant supply of free fatty acids in order to guarantee normal cardiac function, and it further indicates, that the heart is not able to cover its energy demand by switching to glucose oxidation. Since that phenomenon, better known as metabolic inflexibility has been mainly described in patients with diabetes, we aim to investigate the impact of FFA-inhibition on MYCL and cardiac function in patients with overt type 2 diabetes.
Interventions
DRUGacipimox
DRUGPlacebo Oral Capsule
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Type 2 Diabetes * HbA1C \>6%
Exclusion criteria
* Insulin therapy (except: BOT=basal supported oral therapy) * Known heart disease including coronary artery disease, cardiomyopathy, history of cardiac surgery * Known intolerance against niacins * Known contra-indications against magnetic resonance (MR-) examinations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MYCL | 180 minutes | Intramyocardiocellular lipid content (MYCL) before and after administration of acipimox or placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ejection Fraction | 180 minutes | Left ventricular ejection fraction before and after administration of acipimox or placebo |
Other
| Measure | Time frame | Description |
|---|---|---|
| Stroke Volume | 180 minutes | Stroke volume before and after administration of acipimox or placebo |
Countries
Austria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants On study day 1 subjects received acipimox 250 mg or placebo at 0 and 180 minutes (randomized, controlled, single blinded); after a wash out period of at least two weeks on study day 2 i) subjects who received acipimox 250 mg on study day 1 were administered placebo at 0 and 180 minutes and ii) subjects who received placebo on study day 1 were administered acipimox 250 mg at 0 and 180 minutes (randomized, controlled, single blinded). | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 56 years STANDARD_DEVIATION 11 |
| Region of Enrollment Austria | 8 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
MYCL
Intramyocardiocellular lipid content (MYCL) before and after administration of acipimox or placebo
Time frame: 180 minutes
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acipimox+ | MYCL | Baseline | 0.54 percentage of water signal | Standard Deviation 0.1 |
| Acipimox+ | MYCL | 180 minutes after administration | 0.35 percentage of water signal | Standard Deviation 0.2 |
| Placebo | MYCL | Baseline | 0.44 percentage of water signal | Standard Deviation 0.1 |
| Placebo | MYCL | 180 minutes after administration | 0.36 percentage of water signal | Standard Deviation 0.1 |
Secondary
Ejection Fraction
Left ventricular ejection fraction before and after administration of acipimox or placebo
Time frame: 180 minutes
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acipimox+ | Ejection Fraction | Baseline | 76 percentage | Standard Deviation 6 |
| Acipimox+ | Ejection Fraction | 180 minutes after administration | 69 percentage | Standard Deviation 9 |
| Placebo | Ejection Fraction | Baseline | 78 percentage | Standard Deviation 8 |
| Placebo | Ejection Fraction | 180 minutes after administration | 77 percentage | Standard Deviation 7 |
Other Pre-specified
Stroke Volume
Stroke volume before and after administration of acipimox or placebo
Time frame: 180 minutes
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acipimox+ | Stroke Volume | baseline | 38 ml/m2 | Standard Deviation 10 |
| Acipimox+ | Stroke Volume | 180 minutes after administration | 31 ml/m2 | Standard Deviation 8 |
| Placebo | Stroke Volume | baseline | 36 ml/m2 | Standard Deviation 6 |
| Placebo | Stroke Volume | 180 minutes after administration | 36 ml/m2 | Standard Deviation 6 |