Official Title: “Rhubarb and Angiotensin Converting Enzyme Inhibitor”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

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.

Intervention(s) in this Clinical Trial

• Dietary Supplement: rhubarb extract
  • titrate rhubarb extract titrated up to 6grams daily by mouth
• Dietary Supplement: placebo
  • placebo titrated up to 6 pills daily as patient tolerates

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: rhubarb extract
  • will receive rhubarb extract
• Placebo Comparator: placebo
  • receive placebo

Primary Measures

• albuminuria
  • Time Frame: 2 years
    Safety Issue?: No

Secondary Measures

• rate of decline of GFR
  • Time Frame: 2 years
    Safety Issue?: 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Wake Forest University

Overall Clinical Trial Officials and Contacts

John Burkart, MD Principal Investigator Wake Forest University  

Overall Contact: John Burkart, MD 336-716-3963 jburkart@wfubmc.edu

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00672451

Study ID Number: 1R21AT002367-01A2

ClinicalTrials.gov Identifier: NCT00672451

Health Authority: United States: Institutional Review Board