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| ID | Type | Description | Link |
|---|---|---|---|
| K23HL098744 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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Patients with chronic kidney disease have profound exercise intolerance which contributes to an increased risk of cardiovascular disease. The investigators have found that chronic kidney disease patients have an exaggerated increase in blood pressure during certain forms of exercise that could certainly contribute to exercise dysfunction as well as cardiovascular risk. The investigators will test the mechanisms underlying this exaggerated blood pressure response, as well as the potential benefits of short-term tetrahydrobiopterin (BH4) with folic acid on both exercise dysfunction and cardiovascular risk factors in chronic kidney disease. The investigators will test whether short-term treatment with tetrahydrobiopterin (BH4), a cofactor for nitric oxide, together with folic acid improves inflammation, vascular health, and adrenaline levels, both at rest and during exercise in chronic kidney disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tetrahydrobiopterin + Folate | Experimental | Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive Tetrahydrobiopterin (6R-BH4) 200 mg twice daily and folic acid 1 mg daily |
|
| Placebo + Folate | Placebo Comparator | Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive 2 placebo pills twice daily and folic acid 1 mg daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tetrahydrobiopterin | Drug | Tetrahydrobiopterin (BH4) 200 mg PO BID for 12 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Resting Muscle Sympathetic Nerve Activity (MSNA) | Baseline, 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mean Central Augmentation Index (AIx) | The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks. | Baseline, 12 weeks |
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Inclusion Criteria:
chronic kidney disease (CKD) stages I, II, and III and do not regularly exercise
1. CKD Stages I, II, and III will be defined as reduction in estimated glomerular filtration rate (eGFR) to 30-59 cc/minute as calculated by the Modification of Diet in Renal Disease (MDRD) equation, or an eGFR>60 cc/minute with proteinuria greater than 500 mg/g of Creatinine or 500 mg per 24 hours.
willing and able to cooperate with the protocol
CKD patients must have stable renal function (no greater than a 20% reduction in eGFR over the prior 3 months)
controls will be matched for age, gender, race, and hypertensive status.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeanie Park, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University Hospital | Atlanta | Georgia | 30322 | United States | ||
| Atlanta VA Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26962106 | Derived | Lin AM, Liao P, Millson EC, Quyyumi AA, Park J. Tetrahydrobiopterin ameliorates the exaggerated exercise pressor response in patients with chronic kidney disease: a randomized controlled trial. Am J Physiol Renal Physiol. 2016 May 1;310(10):F1016-25. doi: 10.1152/ajprenal.00527.2015. Epub 2016 Mar 9. |
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42 subjects were withdrawn prior to group assignment. 16 were screen failures, 7 subjects withdrew, and 19 subjects were terminated early.
Subjects were recruited from the Atlanta Veterans Affairs (VA) Medical Center from August 2010 to May 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tetrahydrobiopterin + Folate | Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily |
| FG001 | Placebo + Folate | Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All subjects that were randomized in the study are included in baseline analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tetrahydrobiopterin + Folate | Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily |
| BG001 | Placebo + Folate |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Resting Muscle Sympathetic Nerve Activity (MSNA) | Two subjects withdrawn from each arm due to adverse events. Additionally, two subjects from the treatment group and one subject from the placebo group were not included in this analysis because an adequate MSNA neurogram was unable to be obtained at the end of the study. | Posted | Mean | Standard Error | bursts/minute | Baseline, 12 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tetrahydrobiopterin + Folate | Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jeanie Park | Emory University | 404-727-1386 | jeanie.park@emory.edu |
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| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| C003402 | sapropterin |
| D005492 | Folic Acid |
| ID | Term |
|---|---|
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Placebo | Drug | 2 placebo pills PO BID for12 weeks |
|
| Folate | Dietary Supplement | Folate 1 mg daily for 12 weeks |
|
|
| Change in Heart-rate-corrected Augmentation Index (AIx) | The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks. | Baseline, 12 weeks |
| Decatur |
| Georgia |
| 30033 |
| United States |
Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | Change in Mean Central Augmentation Index (AIx) | The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks. | Posted | Mean | Standard Error | percent | Baseline, 12 weeks |
|
|
|
| Secondary | Change in Heart-rate-corrected Augmentation Index (AIx) | The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks. | Posted | Mean | Standard Error | percent | Baseline, 12 weeks |
|
|
|
| 0 |
| 18 |
| 2 |
| 18 |
| EG001 | Placebo + Folate | Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily | 0 | 14 | 2 | 14 |
| Dysgeusia | General disorders |
|
| Acute Kidney Injury | Renal and urinary disorders |
|
| Eye injury | Injury, poisoning and procedural complications |
|
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| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006571 | Heterocyclic Compounds |