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| ID | Type | Description | Link |
|---|---|---|---|
| 2P01HL116263-06 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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The Investigators will test the hypothesis that 2-HOBA will reduce modification of HDL and LDL and improve HDL function in humans with heterozygous FH. The Investigators plan to first study subjects with Familial Hypercholesterolemia (FH), treating them with 750 mg of 2-HOBA or placebo every 8 hours for 6 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 2-Hydroxybenzylamine (2-HOBA) | Active Comparator | 2-Hydroxybenzylamine (2-HOBA) 250 mg three tabs TID (po) for 6 weeks. |
|
| Placebo | Placebo Comparator | Placebo- three tabs TID (po) for 6 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 2-Hydroxybenzylamine | Drug | 2-Hydroxybenzylamine (2-HOBA) 250 mg three tabs TID (po) for 6 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 2-HOBA increases HDL cholesterol efflux capacity. | Change in HDL cholesterol efflux capacity will be measured by macrophage cholesterol efflux assay. | Baseline to week 6 |
| Measure | Description | Time Frame |
|---|---|---|
| 2-HOBA reduces modification of HDL by Isolevuglandin (Iso-LG). | Measurement of the Iso-LG-lysine lactam by mass spectrometry. | Baseline to week 6 |
| 2-HOBA reduces modification of HDL by malondialdehyde (MDA). |
| Measure | Description | Time Frame |
|---|---|---|
| Change in HDL anti-inflammatory function in an in vitro assay of macrophage cytokine production (IL-1B, TNFa, IL-6). | Measurement of changes in LPS-stimulated macrophage cytokine production(IL-1B, TNFa, IL-6). | Baseline to week 6 |
| Change in HDL anti-oxidant function in an in vitro assay of macrophage reactive oxygen species production. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anca Ifrim, RN | Contact | 6155224210 | anca.ifrim@vumc.org |
| Name | Affiliation | Role |
|---|---|---|
| MacRae F. Linton, MD | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Recruiting | Nashville | Tennessee | 37212 | United States |
Individual participant data that underlie the results reported will be made available (including data dictionaries) after de-identification.
The data will become available 3 months following publication of outcomes and will remain available for at least 5 years.
Data will be made available to researchers who provide a methodologically sound proposal that has been approved by the Vanderbilt Institutional Review Board and the study executive committee.
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| ID | Term |
|---|---|
| D006938 | Hyperlipoproteinemia Type II |
| ID | Term |
|---|---|
| D008052 | Lipid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C032416 | 2-(aminomethyl)phenol |
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Subjects will be randomized to treatment with either 2-Hydroxybenzylamine (2-HOBA) , a naturally occuring dicarbonyl scavenger, or placebo for 6 weeks.
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| Placebo | Other | Placebo 250 mg three tabs TID (po) for 6 weeks. |
|
Measurement of dilysyl-MDA cross-links by mass spectrometry.
| Baseline to week 6 |
Measurement of changes in H2O2-stimulated macrophage reactive oxygen species |
| Baseline to week 6 |
| Change in HDL microRNA and small noncoding ribonucleic acid (sRNA) composition | HDL microRNA and sRNA will be measured through high-throughput sequencing with quantitative polymerase chain reaction (qPCR) validation. | Baseline to week 6 |
| Effects of 2-HOBA on HDL and LDL subpopulation sizes | HDL and LDL subpopulation sizes and particle numbers will be measured by NMR | Baseline to week 6 |
| D006951 | Hyperlipoproteinemias |
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |