Clinical trial NCT00234156: The Effect of Fructose on Blood Fats in Dialysis Patients and Healthy Volunteers
Official title: Sensitivity to Fructose-Induced Palmitate Synthesis in End-Stage Renal Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End-stage Renal Disease
Keywords: Fructose
Lipogenesis
Triglycerides
Dialysis
Lead sponsor: Rockefeller University
Sponsor class: OTHER
Collaborators: name: Robert C. Atkins Foundation
name: The Rogosin Institute
First posted: 2005-10-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study will evaluate how a common dietary sugar (fructose) raises blood fats (triglycerides). We will determine whether the production of fat from fructose is higher in dialysis patients compared to healthy volunteers. Dialysis patients have high levels of hormone-like substances called cytokines that may increase blood fats. The results will help set better guidelines for diets for the general population and patients with kidney disease who are at high risk for heart attack and stroke.

There will be one or two outpatient screening visit(s) and a one-week (6 nights) stay at the Rockefeller University Hospital.

Detailed description: Fifteen hemodialysis patients and 15 healthy volunteers will be studied.

Outpatient screening visit(s): consent, fasting blood and urine analysis, a physical exam, an EKG and a 2-hour oral glucose tolerance test to screen for diabetes.

Inpatient admission:

* Standardized diet that follows the guidelines for hemodialysis patients and healthy volunteers to maintain a stable weight.
* Blood and urine sampling. The total amount of blood drawn is less than 1 cup.
* To measure the production of fat from fructose, a trace amount of a non-radioactive labeled precursor of fat (13C-acetate) will be infused through a venous catheter for 22 hours.

At the end of the infusion, a sweet drink (fructose in 1 ounce of water) will be given orally every half hour for 6 hours.

• Two small samples of fat taken right below the skin will be obtained after injection of a small amount of numbing medicine into the abdominal and gluteal regions.

Dialysis patients will receive their usual dialysis at The Rogosin Institute Manhattan, Brooklyn or Queens Dialysis Units.

Eligibility criteria: Inclusion Criteria:

1. Male and females, 18-75 years of age.
2. Chronic renal failure with hemodialysis 3x/week for at least 6 months and adequate dialysis as judged by a nephrologist who is not a study investigator.
3. Fasting TG \<600 mg/dl, LDL cholesterol \<190 mg/dl (off lipid-lowering medication)
4. Willing and able to change Renagel, a noncalcemic phosphate binder (poly\[allylamine hydrochloride\]) which has LDL-lowering effects, to the same amount of another phosphate binder for 1 month prior to the screening visit until the completion of the study.
5. Willing and able to temporarily stop Sensipar (cinacalcet) for 1 week before the study admission until completion of the study (a total of \~2 weeks).
6. Willing and able to stop ASA (except low dose ASA in patients with vascular disease), NSAID, fish oil, psyllium, other nonprescribed vitamins/supplements for 1 week prior to study until completion of study.
7. Willing and able to sign an informed consent.
8. Willing to refrain from participation in an investigational drug study for the duration of the study.

Exclusion Criteria:

1. Diabetes (fasting blood sugar \>126 twice or an abnormal 2 hour OGTT)
2. Unstable clinical condition, including acute febrile illness within 1 month of admission
3. Chronic infection, including hepatitis and HIV infection
4. Gastrointestinal disease resulting in significant GI dysfunction or malabsorption
5. Lipid-lowering medication
6. Mean systolic blood pressure \>180 or diastolic pressure \>110 taken immediately before 6 dialysis treatments over the 2 weeks before the screening visit 7/15/2008 Form version 6/13/2005 #LHU-0471-0407 Page 8of 16f
7. BMI \>35 (markedly obese)
8. Hemoglobin \<10.0
9. Prednisone, estrogen/progesterone, other steroids, Synthroid, endocrine disease
10. Coumadin and an INR \>1.5
11. Cigarette smoking \>1/2 pack/day
12. Abuse of ethanol (greater than 2 drinks/day) or illicit drugs
13. If female, pregnant or breast feeding
14. Participation in a study of an investigational drug during the 30 days preceding the start of the screening period
15. Have any other condition, which in the opinion of the investigator, should prohibit the participation in the study

Healthy Controls:

Inclusion Criteria

1. Male and females, 18-75 years of age 2. LDL \<160 mg/dl, HDL-C \>30 mg/dl, TG \<250 mg/dl 3. Willing and able to stop ASA, NSAID, fish oil, psyllium, other vitamins/supplements for 1 week prior to study until completion of study 4. Willing and able to sign an informed consent 5. Willing to refrain from participation in an investigational drug study for the duration of the study Exclusion Criteria

1. Systemic illnesses, including diabetes (FBS \>126 twice or abnormal OGTT), cardiovascular disease, hepatitis, endocrine disease, HIV infection.
2. Prescription medications, including contraceptives.
3. Acute febrile illness within 1 month of admission.
4. BMI \>35 (markedly obese) or\>10% below maximum weight.
5. Weight change of \>10% usual weight in the previous 6 months.
6. Blood pressure \>140/90.
7. HB \<11 female, \<12 male.
8. CRP \>5.0 on 2 occasions. 7/15/2008 Form version 6/13/2005 #LHU-0471-0407 Page 9of 16f
9. Abuse of ethanol (greater than 2 drinks/day) or illicit drugs.
10. Cigarette smoking \>1/2 pack/day.
11. Unusual diet or extreme physical activity (e.g. marathon runner).
12. If female, pregnant or breast feeding.
13. Participation in a study of an investigational drug during the 30 days preceding the start of the screening period.
14. Have any other condition, which in the opinion of the investigator, should prohibit the participation in the study.

Primary outcomes:
measure: Peak percent de novo palmitate in blood triglycerides after oral fructose
timeFrame: day 1 and day 6
Secondary outcomes:
measure: Relationship between TNF and/or its soluble receptors and % newly formed palmitate
timeFrame: Day 1 and Day 6
measure: fatty acid composition of TG and adipose tissue
timeFrame: Day 1 of hospital admission
Other outcomes:
Locations:
city: New York
country: United States
facility: Rockefeller University Hospital
state: New York
Study officials:
affiliation: Rockefeller University, Rogosin Institute
name: Lisa C. Hudgins, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hudgins LC, Parker TS, Levine DM, Hellerstein MK. A dual sugar challenge test for lipogenic sensitivity to dietary fructose. J Clin Endocrinol Metab. 2011 Mar;96(3):861-8. doi: 10.1210/jc.2010-2007. Epub 2011 Jan 20.