Hypertension, Type 2 Diabetes
Conditions
Keywords
Type 2 Diabetes, Hypertension
Brief summary
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.
Detailed description
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.
Interventions
DRUGamlodipine, 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.
Sponsors
Tulane University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 Diabetes * Hypertension * Estimated glomerular filtration rate (eGFR) \> 30 ml/min * Use of Ace Inh and ARB for control of blood pressure who are willing to be placed on alternate drug(s) in the washout period for blood pressure control
Exclusion criteria
* Pregnancy * Patients with chronic kidney disease stage with eGFR \< 30 ml/min (CKD stage IV and V) * Nephrotic range proteinuria (urinary protein \> 3.5 gm/day) * History or renal transplantation * History of multiple myeloma * Known history of hypersensitivity reaction or intolerability to Ace Inh or ARB.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urine Microalbumin Creatinine Ratio | Visit 1 (Baseline), Visit 3 (Day 60) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Level of Urinary Free Light Chains | Visit 1 (Baseline), Visit 3 (Day 60) | In relation to kidney function and washout/reintroduction of ACE/ARB medication the level of urinary free light chains will be assessed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | Alternate Antihypertensive Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 59.61 years STANDARD_DEVIATION 9.48 |
| Creatinine | 1.01 mg/dL STANDARD_DEVIATION 0.23 |
| eGFR | 72.44 mL/min/1.73m^2 STANDARD_DEVIATION 21.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Hemoglobin A1c | 7.53 Percent STANDARD_DEVIATION 1.07 |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 0 / 28 | 0 / 28 | 0 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 | 0 / 28 |
Outcome results
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.
Time frame: Visit 1 (Baseline), Visit 3 (Day 60)
Population: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alternate Antihypertensive Arm | Change in Urine Microalbumin Creatinine Ratio | 15 mg/g | Standard Deviation 2.5 |
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.
Time frame: Visit 1 (Baseline), Visit 3 (Day 60)
Population: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alternate Antihypertensive Arm | Change in the Level of Urinary Free Light Chains | 1.14 mg/g | Standard Deviation 2.03 |