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Study of Keto Acid (KA) on Insulin Resistance in Peritoneal Dialysis (PD) Patients

This study has been completed.
Sponsor:
Collaborator:
Vanderbilt University
Information provided by (Responsible Party):
Dong Jie, Peking University First Hospital
ClinicalTrials.gov Identifier:
NCT01496092
First received: August 19, 2011
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

The overarching aim of this proposal is to examine the effects of usual protein diet supplemented with keto acid (KA) on insulin sensitivity in patients on peritoneal dialysis (PD). The investigators will achieve this goal through a randomized controlled trial of administration of usual protein diet plus KA versus usual protein diet alone in patients on peritoneal dialysis (PD) over a period of 6 months. If successful, the results of this study will provide potential avenues for improvement of metabolic profile of patients on PD and possibly improve long-term outcomes such as cardiovascular disease risk and death.


Condition Intervention Phase
Insulin Resistance
Drug: Keto Acid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Regular Protein Diet Supplemented With Keto Acid on Insulin Resistance In Peritoneal Dialysis Patients

Resource links provided by NLM:


Further study details as provided by Peking University First Hospital:

Primary Outcome Measures:
  • Insulin resistance [ Time Frame: at 0, 12, 24 week after patients start their study prescription ] [ Designated as safety issue: Yes ]
    Insulin sensitivity will be measured using HOMA-IR.


Secondary Outcome Measures:
  • Oxidative stress [ Time Frame: at 0, 12, 24 week after patients start their study prescription ] [ Designated as safety issue: Yes ]
    Oxidative stress will be assessed by Plasma OxLDL.

  • Inflammatory state [ Time Frame: at 0, 12, 24 week after patients start their study prescription ] [ Designated as safety issue: Yes ]
    Inflammatory state will be assessed by C-reactive protein, pro-inflammatory cytokine levels (IL-6) and adipokines (leptin and adiponectin).

  • Endothelial dysfunction [ Time Frame: at 0, 12, 24 week after patients start their study prescription ] [ Designated as safety issue: Yes ]
    sICAM and sVCAM will be measured.


Enrollment: 100
Study Start Date: April 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Keto Acid supplemented with usual protein diet Drug: Keto Acid
12 tablets per day
Other Name: Compound α-Ketoacid Tablets
No Intervention: usual protein diet

Detailed Description:

Specific Aims and Significance:

To evaluate the effects of KA plus usual protein diet on basal and stimulated insulin sensitivity in PD patients.

Hypothesis: Administration of KA plus usual protein diet will improve insulin resistance in peritoneal dialysis patients.

To evaluate the influence of KA plus usual protein diet on non-traditional cardiovascular disease (CVD) markers (markers of inflammation and oxidative stress) in PD patients.

Hypothesis: Administration of KA plus usual protein diet will improve markers of inflammation and oxidative stress in PD patients.

Background and Rationale:

Insulin Resistance in Peritoneal Dialysis Patients. Insulin resistance (IR), the reciprocal of insulin sensitivity, describes a state of reduced biological effect for any given concentration of insulin in the plasma. Insulin resistance plays a major pathophysiological role in glucose intolerance and Type 2 diabetes mellitus (T2DM) and is tightly associated with major public health problems including obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Insulin resistance, measured by homeostatic model assessment (HOMA-IR), is reported to be common in chronic kidney disease (CKD) patients, including ones on PD and hemodialysis (HD). HOMA-IR is also shown to be an independent predictor of cardiovascular mortality in non-diabetic maintenance HD patients although the pathophysiological link has not been clearly delineated.

A unique aspect of PD that predisposes patients to IR is the inevitable glucose load from the dialysate required for ultrafiltration. Consequently, the prevalence of metabolic syndrome such as hyperglycemia, dyslipidemia and weight gain is increased in PD patients. As an individual component of metabolic syndrome, IR is significantly higher in PD patients than in HD or pre-dialysis patients (47% vs 21% or 26%). Accordingly, improvement of IR could be a potential intervention to decrease the CVD risk and mortality in PD patients. However, only a few investigations have centered on interventions to ameliorate IR in these patients.

Low Protein Diet Supplemented with Keto Acid as a Potential Strategy to Ameliorate Insulin Resistance in PD Patients. Several small scale studies exploring the effects of low protein diet (LPD) plus KA on glucose metabolism indicated that LPD-KA could improve liver and peripheral tissue insulin sensitivity in CKD patients not yet on maintenance dialysis. There are no studies exploring such effects in maintenance dialysis patients, especially in PD patients. One potential mechanism for the improvement in insulin resistance by KA is the reduction of circulating uremic toxins, although the specific elements are not well delineated. In addition, the supplementation of KA might be helpful since plasma total branched-chain amino acid concentrations correlate with glucose tolerance index in dialysis patients. Since the safety of LPD has not been entirely shown in previous studies for PD patients, and our data indicated that DPI < 0.74g/kg/d was harmful in the long-term PD, the investigators will not provide the LPD for improving the IR. However, the exploration of possible benefits of KA plus usual protein intake in PD patients on insulin sensitivity is intriguing.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • medically stable and receiving stable PD >= 3 months
  • age 18-80 years
  • body mass index > 18.5
  • Kt/v >= 1.7 or Tccr >= 50l/week/1.73m2
  • glucose lactate-buffered PD solutions

Exclusion Criteria:

  • pregnancy
  • intolerance to the study protocols
  • severe, unstable, active, or chronic inflammation disease
  • chronic use of anti-inflammatory medication
  • severe malnutrition
  • a high probability of receiving a kidney transplant or transferring to HD within 6 months
  • taking anti-inflammatory medication chronically or taking KA during the past one month
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01496092

Locations
China, Beijing
Jie Dong
Beijing, Beijing, China, 100034
Sponsors and Collaborators
Peking University First Hospital
Vanderbilt University
Investigators
Principal Investigator: Jie Dong, MD,PhD Peking University First Hospital
  More Information

No publications provided

Responsible Party: Dong Jie, Institute of Nephrology, Division of Renal, Peking University First Hospital
ClinicalTrials.gov Identifier: NCT01496092     History of Changes
Other Study ID Numbers: KAPD
Study First Received: August 19, 2011
Last Updated: February 19, 2014
Health Authority: China: Ethics Committee

Keywords provided by Peking University First Hospital:
Keto Acid
Peritoneal dialysis
Insulin resistance

Additional relevant MeSH terms:
Insulin Resistance
Glucose Metabolism Disorders
Hyperinsulinism
Metabolic Diseases
Insulin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 23, 2014