Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy

A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Trial of Uridine Supplementation in HIV Lipoatrophy

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00307164

Enrollment

167

Registered

2006-03-27

Start date

2006-09-30

Completion date

2008-12-31

Last updated

2021-11-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV Infections, Lipoatrophy

Keywords

Treatment Experienced, Uridine

Brief summary

Lipoatrophy, the loss of body fat from particular areas of the body, is a common side effect of antiretroviral therapy (ART). The purpose of this study was to determine the effectiveness of uridine supplementation in treating HIV infected individuals on stable ART with lipoatrophy.

Detailed description

Lipoatrophy is a distressing long-term complication of ART and is associated with decreased quality of life, an increased risk of cardiovascular disease, and nonadherence to ART. The cause of lipoatrophy in HIV-infected individuals receiving ART is not completely understood. However, past research suggests that mitochondrial toxicity in subcutaneous adipose tissue caused by thymidine analogue nucleoside analogues may be responsible for the development of lipoatrophy. Uridine is a nucleoside that has been shown to be an effective supplement in treating individuals with mitochondrial toxicity. NucleomaxX is a food supplement that consists of mitocnol, a sugar cane extract that has a high content of nucleosides, including uridine. The purpose of this study was to evaluate the effects of uridine supplementation in the form of NucleomaxX on limb fat in HIV-infected individuals receiving stable ART containing stavudine (d4T) or zidovudine (ZDV). In addition, this study evaluated the safety and tolerability of NucleomaxX. This study lasted for 48 weeks. Participants were randomly assigned to one of two treatment arms, stratified by d4T or ZDV use. Arm A participants received NucleomaxX for uridine, while Arm B participants received a placebo for NucleomaxX. Participants in both arms received their assigned intervention three times per day, every other day, for the duration of the study. There were 8 study visits over the 48-week study duration. Blood collection and a physical exam occurred at all study visits, and participants completed an adherence assessment at most visits. Participants underwent dual energy X-ray absorptiometry scans (DEXA) within 14 days prior to or following the screening visit and at other selected visits. Specific fasting tests for glucose and lipid levels occurred at selected visits. ART was not provided by this study.

Interventions

DRUGNucleomaxX

36 g sachet taken orally three times daily

DRUGNucleomaxX placebo

36 g placebo sachet taken orally three times daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Caregiver)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* HIV-1 infected * Stable ART containing zidovudine or stavudine for at least 12 consecutive weeks prior to study entry * Cumulative ART with zidovudine or stavudine for at least 24 weeks prior to study entry * Viral load of 5,000 copies/ml or less within 45 days prior to study entry * Lipoatrophy in at least two of the following areas: face, arms, legs, OR buttocks * Not planning to add to or change current vitamin supplementation * Willing to use acceptable forms of contraception

Exclusion criteria

* Life expectancy of less than 12 months * Currently enrolled in or planning to enroll in an ART interruption study * Plans to change current ART regimen * Liver failure at anytime prior to study entry * Greater than Grade 2 diarrhea or vomiting within 7 days prior to study entry * Current AIDS-defining opportunistic infection or illness. Individuals with cutaneous Kaposi's sarcoma not requiring chemotherapy are not excluded. * Currently receiving insulin or oral hypoglycemic products for diabetes mellitus * Systemic cancer chemotherapy or immunomodulating agents within 30 days prior to study entry * Systemic steroids for a cumulative duration of longer than 4 weeks within the 6 months prior to study entry * Known allergy or sensitivity to study drug or any of its components * Severe lactose intolerance * Current drug or alcohol abuse or dependence * Clinically significant illness requiring systemic treatment or hospitalization * Chronic disability or serious illness that may affect body composition * Received an investigational drug other than NucleomaxX or uridine for lipoatrophy within 30 days prior to study entry * Certain abnormal laboratory values * Pregnancy or breastfeeding

Design outcomes

Primary

Measure	Time frame	Description
Change in Limb Fat (g) From Baseline	Baseline and Week 48	Limb fat was measured at baseline and visit week 48 using dual-energy x-ray absorptiometry (DEXA), and change from baseline to week 48 (week 48 - baseline) was estimated for the treatment groups.

Secondary

Measure	Time frame	Description
Number of Subjects Discontinuing Study Medication	Through Week 48	Number of eligible subjects who discontinued study medication during the study period.
Change in Limb Fat From Baseline (Week 24 - Baseline)	Baseline and Week 24	Limb fat was measured at baseline and visit week 24 using dual-energy x-ray absorptiometry (DEXA), and change from baseline to week 24 (week 24 - baseline) was estimated for the treatment groups.
HIV-1 RNA Level	At Week 48	—
Change in CD4+ Count From Baseline (Week 48 - Baseline)	Baseline and Week 48	—
Change in Fasting Lactate From Baseline (Week 48 - Baseline)	Baseline and Week 48	—
Change in Fasting Glucose From Baseline (Week 48 - Baseline)	Baseline and Week 48	—
Change in Fasting Total Cholesterol From Baseline (Week 48 - Baseline)	Baseline and Week 48	—
Time to Safety Events (Signs/Symptoms or Laboratory Abnormalities)	Through Week 48	Time to safety events (grade 3 \[Severe\] or 4 \[life-threatening\] sign/symptom or laboratory-based abnormality that is at least one grade higher than baseline) from study entry
Change in Fasting Non-HDL Cholesterol From Baseline (Week 48 - Baseline)	Baseline and Week 48	—
Change in Fasting Low-density Lipoprotein (LDL) Cholesterol From Baseline (Week 48 - Baseline)	Baseline and Week 48	—
Change in Fasting Triglycerides From Baseline (Week 48 - Baseline)	Baseline and Week 48	—
Change in Hemoglobin From Baseline (Week 48 - Baseline)	Baseline and Week 48	—
Change in Leukocytes From Baseline (Week 48 - Baseline)	Baseline and Week 48	—
Change in Creatine Kinase From Baseline (Week 48 - Baseline)	Baseline and Week 48	—
Change in Fasting High-density Lipoprotein (HDL) Cholesterol From Baseline (Week 48 - Baseline)	Baseline and Week 48	—

Countries

Puerto Rico, United States

Participant flow

Recruitment details

Recruited at AIDS Clinical Trials Units in the United States and Puerto Rico. Recruitment occurred between October 5, 2006 (date first subject was randomized) and January 7, 2008 (date last subject was randomized).

Pre-assignment details

A total of 167 subjects were randomized, and results are reported for 165 eligible participants; two subjects never started study medication and were excluded from all analyses. The subjects were stratified by antiretroviral therapy use, stavudine (d4T) or zidovudine (AZT/ZDV).

Participants by arm

Arm	Count
NucleomaxX Participants received NucleomaxX for uridine through week 48	83
Placebo Participants received NucleomaxX placebo through week 48	82
Total	165

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	1	0
Overall Study	Lost to Follow-up	6	1
Overall Study	Not compliant with requirements	4	4
Overall Study	Severe debilitation, unable to continue	1	0
Overall Study	Subject/parent not able to get to clinic	2	1
Overall Study	Withdrawal by Subject	1	8

Baseline characteristics

Characteristic	NucleomaxX	Placebo	Total
Age, Continuous	48.4 years STANDARD_DEVIATION 7.78	48.4 years STANDARD_DEVIATION 6.46	48.4 years STANDARD_DEVIATION 7.13
Age, Customized 30-39 Years	9 Participants	10 Participants	19 Participants
Age, Customized 40-49 Years	38 Participants	32 Participants	70 Participants
Age, Customized 50-59 Years	28 Participants	38 Participants	66 Participants
Age, Customized 60-69 Years	8 Participants	2 Participants	10 Participants
Antiretroviral Therapy Used (Stratification) AZT-Containing	63 Participants	63 Participants	126 Participants
Antiretroviral Therapy Used (Stratification) d4T-Containing	20 Participants	19 Participants	39 Participants
CD4+ Count (NucleomaxX sample size (N)=80, Placebo N=80)	506 Cells/mm^3	504 Cells/mm^3	506 Cells/mm^3
Creatine kinase (NucleomaxX N=80, Placebo N=82)	125 IU/L	142 IU/L	134 IU/L
Fasting glucose (NucleomaxX N=82, Placebo N=82)	90 mg/dL	87 mg/dL	89 mg/dL
Fasting high-density lipoprotein (HDL) (NucleomaxX N=82, Placebo N=80)	39 mg/dL	37 mg/dL	38 mg/dL
Fasting lactate (NucleomaxX N=76, Placebo N=75)	1.3 mmol/L	1.2 mmol/L	1.3 mmol/L
Fasting low-density lipoprotein (LDL) (NucleomaxX N=73, Placebo N=67)	107 mg/dL	110 mg/dL	109 mg/dL
Fasting non-high-density lipoprotein (non-HDL) (NucleomaxX N=77, Placebo N=69)	139 mg/dL	145 mg/dL	143 mg/dL
Fasting total cholesterol (NucleomaxX N=82, Placebo N=81)	194 mg/dL	190 mg/dL	193 mg/dL
Fasting triglycerides (NucleomaxX N=82, Placebo N=81)	161 mg/dL	165 mg/dL	164 mg/dL
Hemoglobin	14.9 g/dL	15.0 g/dL	14.9 g/dL
HIV-1 RNA (copies/mL) Category <=50 Copies	70 Participants	64 Participants	134 Participants
HIV-1 RNA (copies/mL) Category >50 Copies	13 Participants	18 Participants	31 Participants
Leukocytes	5.6 cells*10^3/L	5.5 cells*10^3/L	5.5 cells*10^3/L
Limb fat	3149 Grams	2995 Grams	3037 Grams
Race/Ethnicity, Customized Asian, Pacific Islander	3 Participants	1 Participants	4 Participants
Race/Ethnicity, Customized Black Non-Hispanic	11 Participants	14 Participants	25 Participants
Race/Ethnicity, Customized Hispanic (Regardless of Race)	15 Participants	12 Participants	27 Participants
Race/Ethnicity, Customized Native American, Alaskan Native	3 Participants	2 Participants	5 Participants
Race/Ethnicity, Customized Other (More than One Race)	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Unknown	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized White Non-Hispanic	50 Participants	52 Participants	102 Participants
Region of Enrollment Puerto Rico	2 participants	1 participants	3 participants
Region of Enrollment United States	81 participants	81 participants	162 participants
Sex: Female, Male Female	8 Participants	7 Participants	15 Participants
Sex: Female, Male Male	75 Participants	75 Participants	150 Participants
Trunk fat	8175 Grams	7795 Grams	8114 Grams

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	75 / 83	70 / 82
serious Total, serious adverse events	4 / 83	2 / 82

Outcome results

Primary

Change in Limb Fat (g) From Baseline

Limb fat was measured at baseline and visit week 48 using dual-energy x-ray absorptiometry (DEXA), and change from baseline to week 48 (week 48 - baseline) was estimated for the treatment groups.