Diabetic Kidney Disease
Conditions
Keywords
diabetic kidney disease, albuminuria
Brief summary
Rhubarb extract is a chinese herbal preparation that is used in china and other asian countries to treat constipation and chronic kidney disease. Use of angiotensin converting enzyme inhibitors (ACEI) in diabetic kidney disease has been shown to be beneficial in slowing progression. The purpose of this study is to determine the combined effect of rhubarb plus enalapril (an ACEI)in slowing the rate of decline of CKD in people with kidney disease from diabetes.
Detailed description
Use of angiotensin converting enzyme inhibitors (ACEI) in diabetic nephropathy has been shown to be beneficial in slowing progression of disease. This would include use of ACEI, aggressive blood pressure and blood sugar control as well as other possible interventions. Experimental studies in chronic kidney disease (CKD) patients in China has suggested that rhubarb extract when used alone is equivalent to the protection afforded by ACEI. Furthermore when used in combination with ACEI, the renoprotective effect of rhubarb appears to be additive. Rhubarb extract is a chinese herbal preparation that is used extensively in china and other asian countries to treat constipation and CKD. Its mechanism of action in preventing progression of CKD is uncertain but perhaps related to TGF beta and TNF alpha inhibition. The specific aim is to determine the combined effect of rhubarb plus enalapril slowing the rate of decline of CKD (using Iothalamate GFRs) in patients in diabetes. A secondary aim would be to measure serum TGF beta concentrations over time and see if any observed decrease in the rate of decline of CKD is related to changes in TGF beta levels.
Interventions
DIETARY_SUPPLEMENTrhubarb extract
titrate rhubarb extract titrated up to 6grams daily by mouth
DIETARY_SUPPLEMENTplacebo
placebo titrated up to 6 pills daily as patient tolerates
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Wake Forest University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients \>18 years 2. Patients with diabetic nephropathy (history of type 1 or type 2 diabetes for \> 7 years, no other cause for proteinuria listed in their medical chart). This is the definition used in most peer-reviewed trials44,45 of diabetic nephropathy. We do recognize that their proteinuria could be due to some other concomitant kidney disease but the only way to confirm that is to do a kidney biopsy which is not clinically justified. 3. Proteinuria ≥ 0.5 g/day 4. Ability to sign consent form
Exclusion criteria
1. Pre study GFR (see section 10.7) \< 20 ml/min 2. Renal disease of etiologies other than diabetes 3. Uncontrolled hypertension (Systolic BP \>180 mmHg and Diastolic BP \>110mm Hg) 4. Patients with history of kidney stones in past 10 years 5. Patients with active chronic liver disease (Liver enzymes ALT, AST \>2.5 times normal) 6. Patients with primary small bowel disease with malabsorption, blind loop syndrome, or jejunoileal bypass surgery (may cause unabsorbed fatty acids to combine with calcium which in turn causes too much absorption of oxalate) 7. Patients with current alcohol, illicit drug use or any other condition (eg. Psychiatry disorder) that in the opinion of the investigator may interfere with the patient's ability to comply with the study 8. Pregnant women or women of child bearing potential who are unwilling to use an adequate form of contraceptive during the course of the study (ACEI may be fetotoxic) 9. Patients with significant unstable cardiovascular disease (NYHA class III and IV) 10. Patients with active malignancy 11. Uncontrolled infections. 12. Patients with a known sensitivity to the study medications (including enalapril) 13. Patients on angiotensin II receptor blockers (ARBs) 14. Microscopic or macroscopic hematuria (to rule out kidney disease other than diabetic nephropathy) 15. Patients on any herbal supplements unwilling to discontinue them 16. Severe malnutrition (serum albumin \<2.6mg/dL) 17. Hyperkalemia at baseline, defined as serum potassium ≥ 5.5 mg/dL 18. Iodine allergy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Albumin Concentration in Urine | up to 15 months |
Secondary
| Measure | Time frame |
|---|---|
| Rate of Decline of GFR | 2 years |
Countries
United States
Participant flow
Pre-assignment details
5 Participants were not included in the study analysis or assigned to a group prior to termination.
Participants by arm
| Arm | Count |
|---|---|
| Rhubarb Extract will receive rhubarb extract
rhubarb extract: titrate rhubarb extract titrated up to 6grams daily by mouth | 1 |
| Placebo receive placebo
placebo: placebo titrated up to 6 pills daily as patient tolerates | 2 |
| Total | 3 |
Baseline characteristics
| Characteristic | Rhubarb Extract | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 0 / 1 | 0 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 2 |
Outcome results
Primary
Albumin Concentration in Urine
Time frame: up to 15 months
Population: Data not collected in all participants of the placebo group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rhubarb Extract | Albumin Concentration in Urine | .3 mg/dL | Standard Deviation 0 |
| Placebo | Albumin Concentration in Urine | 7.9 mg/dL | Standard Deviation 0 |
Secondary
Rate of Decline of GFR
Time frame: 2 years
Population: No data collected