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The purpose of this study is to study the effect of blocking the renin angiotensin system on urinary free light chain excretion as compared to urine microalbumin creatinine ratio in subjects with type 2 diabetes. The long term goal is to assess urinary free-light chains as a biomarker of earlier detection of kidney function impairment in subjects with diabetes mellitus.
Free light chains (FLCs) are low-molecular-mass molecules (kappa and lambda light chains), which are by-products of normal immunoglobulin synthesis and are normally excreted through the kidneys. Presence of light chains in the urine is a marker of tubular dysfunction. In patients with impaired kidney function, serum concentrations and urinary excretion of polyclonal FLCs have been noted to be increased. Increased excretion of FLCs and other low-molecular weight proteins [cystatin C, NGAL] in the urine may contribute to progression of chronic kidney disease. Higher Cystatin C has been demonstrated to be related to development of albuminuria. Neutrophil gelatinase-associated lipcalin (NGAL) excretion in the urine is a marker of tubular injury in the kidney and has been shown to be elevated in subjects with type 1 and 2 diabetes mellitus (DM). Angiotensin-converting enzyme inhibitors (Ace Inh) and angiotensin II receptor blockers (ARB) class of drugs are renoprotective in nature and are the first line therapy for treatment of diabetic nephropathy. There is no longitudinal data evaluating the effect of Ace Inh and ARB class of drugs on urinary FLCs (UFLCs).
Our hypothesis is that UFLCs are increased in patients with DM with and without kidney disease and that treatment with Ace Inh and/or ARB will decrease UFLCs in these patients. Additionally, we will explore the change in other low molecular weight proteins [cystatin C, and NGAL] in response to treatment with Ace Inh and ARB.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Washout Period for 30 days | Other | In the washout period, the Ace Inh or ARB classes of medicine(s) that are part of the patient's antihypertensive regimen will be discontinued. The patient will be started on alternative therapy with medications that are approved by the Food and Drug Administration for treatment of high blood pressure (such as amlodipine, hydralazine, terazosin or Hydrochlorothiazide) for control of their blood pressure. The goal for their blood pressure will be set at < 140/90 mm/Hg. The washout period will last for four weeks at the end of which the patient will enter the test period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| amlodipine, hydralazine, terazosin or hydrochlorothiazide | Drug | In the washout period, the Ace Inh or ARB classes of medicine(s) that are part of the patient's antihypertensive regimen will be discontinued. The patient will be started on alternative therapy with medications that are approved by the Food and Drug Administration for treatment of high blood pressure (such as amlodipine, hydralazine, terazosin or Hydrochlorothiazide) for control of their blood pressure. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Urine Microalbumin Creatinine Ratio | Kidney function will be assessed throughout the study to assess changes in function prior to the washout of ACE/ARB medication and reintroduction of the ACE/ARB medication. | Visit 1 (Baseline), Visit 3 (Day 60) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the Level of Urinary Free Light Chains | In relation to kidney function and washout/reintroduction of ACE/ARB medication the level of urinary free light chains will be assessed. | Visit 1 (Baseline), Visit 3 (Day 60) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vechi Batuman, MD | Tulane University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tulane University Health Sciences Center | New Orleans | Louisiana | 70112 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Alternate Antihypertensive Arm | In the washout period, the Ace Inh or ARB classes of medicine(s) that are part of the patient's antihypertensive regimen will be discontinued. The patient will be started on alternative therapy with medications that are approved by the Food and Drug Administration for treatment of high blood pressure (such as amlodipine, hydralazine, terazosin or Hydrochlorothiazide) for control of their blood pressure. The goal for their blood pressure will be set at < 140/90 mm/Hg. The washout period will last for four weeks at the end of which the patient will enter the test period. amlodipine, hydralazine, terazosin or hydrochlorothiazide: In the washout period, the Ace Inh or ARB classes of medicine(s) that are part of the patient's antihypertensive regimen will be discontinued. The patient will be started on alternative therapy with medications that are approved by the Food and Drug Administration for treatment of high blood pressure (such as amlodipine, hydralazine, terazosin or Hydrochlorothiazide) for control of their blood pressure. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Pre RAS Blockade Washout Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 11, 2011 |
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| COMPLETED |
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| NOT COMPLETED |
|
| RAS Blockade Washout Period |
|
| Post RAS Blockade Washout Period |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Alternate Antihypertensive Arm | In the washout period, the Ace Inh or ARB classes of medicine(s) that are part of the patient's antihypertensive regimen will be discontinued. The patient will be started on alternative therapy with medications that are approved by the Food and Drug Administration for treatment of high blood pressure (such as amlodipine, hydralazine, terazosin or Hydrochlorothiazide) for control of their blood pressure. The goal for their blood pressure will be set at < 140/90 mm/Hg. The washout period will last for four weeks at the end of which the patient will enter the test period. amlodipine, hydralazine, terazosin or hydrochlorothiazide: In the washout period, the Ace Inh or ARB classes of medicine(s) that are part of the patient's antihypertensive regimen will be discontinued. The patient will be started on alternative therapy with medications that are approved by the Food and Drug Administration for treatment of high blood pressure (such as amlodipine, hydralazine, terazosin or Hydrochlorothiazide) for control of their blood pressure. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||||
| Creatinine | Mean | Standard Deviation | mg/dL |
| |||||||||||||||||||
| eGFR | Mean | Standard Deviation | mL/min/1.73m^2 |
| |||||||||||||||||||
| Hemoglobin A1c | Mean | Standard Deviation | Percent |
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| 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 Urine Microalbumin Creatinine Ratio | Kidney function will be assessed throughout the study to assess changes in function prior to the washout of ACE/ARB medication and reintroduction of the ACE/ARB medication. | Measurement was done for the change between Visit 1 (screening visit and the beginning of the washout period may be combined -day -30), and Visit 3 (day 30 of the test period). | Posted | Mean | Standard Deviation | mg/g | Visit 1 (Baseline), Visit 3 (Day 60) |
|
|
| |||||||||||||||||||||||||
| Secondary | Change in the Level of Urinary Free Light Chains | In relation to kidney function and washout/reintroduction of ACE/ARB medication the level of urinary free light chains will be assessed. | Measurement was done for the change between Visit 1 (screening visit and the beginning of the washout period may be combined -day -30), and Visit 3 (day 30 of the test period). | Posted | Mean | Standard Deviation | mg/g | Visit 1 (Baseline), Visit 3 (Day 60) |
|
3 years
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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 | Alternate Antihypertensive (Pre RAS Blockade Washout Period) | Patients underwent screening visits and continued their original antihypertensive regimens before they entered the washout period. | 0 | 28 | 0 | 28 | 0 | 28 |
| EG001 | Alternate Antihypertensive (RAS Blockade Washout Period) | In the washout period, the Ace Inh or ARB classes of medicine(s) that are part of the patient's antihypertensive regimen will be discontinued. The patient will be started on alternative therapy with medications that are approved by the Food and Drug Administration for treatment of high blood pressure (such as amlodipine, hydralazine, terazosin or Hydrochlorothiazide) for control of their blood pressure. The goal for their blood pressure will be set at < 140/90 mm/Hg. The washout period will last for four weeks at the end of which the patient will enter the test period. amlodipine, hydralazine, terazosin or hydrochlorothiazide: In the washout period, the Ace Inh or ARB classes of medicine(s) that are part of the patient's antihypertensive regimen will be discontinued. The patient will be started on alternative therapy with medications that are approved by the Food and Drug Administration for treatment of high blood pressure (such as amlodipine, hydralazine, terazosin or Hydrochlorothiazide) for control of their blood pressure. | 0 | 28 | 0 | 28 | 0 | 28 |
| EG002 | Alternate Antihypertensive (Post RAS Blockade Washout Period) | Patients were restarted on their original antihypertensive medication which they were taking when they entered the study | 0 | 28 | 0 | 28 | 0 | 28 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vechi Batuman | Tulane University | (504)988-5346 | vbatuma@tulane.edu |
| Mar 31, 2022 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D017311 | Amlodipine |
| D006830 | Hydralazine |
| C041226 | Terazosin |
| D006852 | Hydrochlorothiazide |
| ID | Term |
|---|---|
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010793 | Phthalazines |
| D011724 | Pyridazines |
| D002740 | Chlorothiazide |
| D001581 | Benzothiadiazines |
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D049971 | Thiazides |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Unknown or Not Reported |
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| Units | Counts |
|---|---|
| Participants |
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