Clinical trial NCT00126308: Facial Lipoatrophy Trial: Immediate Versus Deferred Injections of Poly-L-Lactic Acid for HIV Facial Lipoatrophy
Official title: A Multi-Centre, Open-Label, Randomised Study to Assess the Efficacy, Durability and Safety of Immediate Versus Deferred Injections of Poly-L-Lactic Acid for HIV Facial Lipoatrophy (FLASH)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: HIV-Associated Lipodystrophy
HIV Infections
Keywords: HIV
Lipodystrophy
Intervention
Poly-L-lactic acid
HIV facial lipoatrophy
Treatment Experienced
Lead sponsor: Kirby Institute
Sponsor class: OTHER_GOV
Collaborators: name: The University of New South Wales
name: Abbott
name: Bristol-Myers Squibb
name: Gilead Sciences
name: GlaxoSmithKline
name: Merck Sharp & Dohme LLC
name: Hoffmann-La Roche
name: AIDS Council of New South Wales
First posted: 2005-08-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-centre, open-label, 96 week study to evaluate the safety, tolerability and extent and duration of improvement in HIV-1 infected subjects with antiretroviral induced facial lipoatrophy, randomised in a 1:1 ratio to receive immediate or deferred deep subcutaneous injections of poly-L-lactic acid (PLA). Subjects will receive 4 treatments of PLA approximately every 2nd week, either at trial entry or following a delay period of 24 weeks.

Detailed description: HIV lipodystrophy can be distressing and result in suboptimal antiretroviral (ART) adherence. Physical changes may stigmatise subjects while the negative psychological and social impact has become a major concern. To date, as there is no proven therapy for lipoatrophy, cosmetic interventions for facial lipoatrophy are being studied. Poly-L-lactic acid (PLA) has been shown to be both safe and effective when administered by injection to facial areas.

Study aims are:

1. to evaluate the extent and duration of improvement in HIV facial lipoatrophy of PLA injections;
2. to evaluate the impact of PLA injections on quality of life and ART adherence in subjects with HIV facial lipoatrophy;
3. to evaluate the safety and tolerability of polylactic acid.

100 HIV-infected ART-experienced subjects with facial lipoatrophy will be randomised in a 1:1 ratio at study entry to receive either immediate or deferred treatment (delayed 24 weeks) treatment with PLA. Randomisation will be stratified by age, severity of facial lipoatrophy, current ART (PI or non-PI containing and thymidine- or non-thymidine-containing) and surgeon.

The study has clinical end points monitoring CD4 cell counts, viral loads and adverse events. The study also has psychosocial end points monitoring quality of life.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or more with laboratory evidence of HIV-1 infection
* Received combination antiretroviral therapy (minimum of 2 agents)
* Antiretroviral regimen should be stable for at least 12 weeks prior to entry with no changes planned during the first 48 weeks. For subjects not on antiretroviral therapy at entry there should be no intent to commence therapy in first 24 weeks.
* Moderate or severe facial lipoatrophy and lipodystrophy at one or more other sites
* Provide written, informed consent.

Exclusion Criteria:

* Active AIDS-defining illness including active HIV wasting
* Active herpes labialis or any acute or currently present chronic skin disease (infection/inflammation) on/near area to be treated
* Currently on anticoagulants or any coagulopathy that would preclude safe deep subcutaneous injections
* Women: pregnant, breastfeeding or have positive pregnancy test or not willing to use adequate contraception if of child-bearing potential
* Concomitant therapy with anabolic steroids (except testosterone replacement), corticosteroids at greater than replacement doses, growth hormone or any currently available or experimental agent to improve appetite or weight
* Testosterone replacement for less than 6 months or at greater than replacement doses
* Subjects who have discontinued any prohibited concomitant agent/s must cease this therapy at least 30 days prior to screening.
* Prior use of any facial dermal filling/tissue expansion agent/s
* Any condition which may interfere with ability to comply with study requirements.

Primary outcomes:
measure: The primary endpoint at 24 weeks will be change from baseline in facial soft tissue volume as measured by spiral computed tomography (CT).
timeFrame: 24 weeks
Secondary outcomes:
measure: Change from baseline at week 96 in facial soft tissue volume as measured by spiral CT scan
timeFrame: 96 weeks
measure: Change from baseline at weeks 24 and 96 in physician and patient assessment of facial lipoatrophy severity
timeFrame: 24 and 96 weeks
measure: Change from baseline at weeks 24 and 96 in peripheral fat as assessed by dual-energy X-ray absorptiometry (DEXA)
timeFrame: 24 and 96 weeks
measure: Change from baseline at weeks 24 and 96 in quality of life
timeFrame: 24 and 96 weeks
measure: Change from baseline at weeks 24 and 96 in antiretroviral therapy (ART) adherence and plasma HIV-RNA
timeFrame: 24 and 96 weeks
measure: All serious, grade 3 or 4 clinical adverse events and any adverse event leading to change/s in ART or discontinuation of PLA
timeFrame: 24 and 96 weeks
measure: All serious, grade 3 or 4 clinical adverse events (AEs) and any event leading to change/s in ART reported to week 96
timeFrame: 96 weeks
measure: All AEs attributable to study treatment reported to week 96
timeFrame: week 96
Other outcomes:
Locations:
city: Burwood
country: Australia
facility: Dr Doong's Surgery
state: New South Wales
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Sydney
country: Australia
facility: 407 Doctors
state: New South Wales
city: Sydney
country: Australia
facility: AIDS Research Initiative
state: New South Wales
city: Sydney
country: Australia
facility: Albion Street Clinic
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House General Practice
state: New South Wales
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Taylor Square Private Clinic
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Liverpool Health Service
state: New South Wales
city: Sydney
country: Australia
facility: Waratah Clinic, St. George Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Queensland Health - AIDS Medical Unit
state: Queensland
city: Brisbane
country: Australia
facility: Gladstone Road Medical Centre
state: Queensland
city: Gold Coast
country: Australia
facility: Gold Coast Sexual Health Clinic
state: Queensland
city: Nambour
country: Australia
facility: Clinic 87
state: Queensland
city: Adelaide
country: Australia
facility: The Care and Prevention Programme - Adelaide University
state: South Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
Study officials:
affiliation: Immunology and Infectious Disease Unit, St. Vincent's Hospital, Sydney
name: Andrew Carr, A/Prof
role: PRINCIPAL_INVESTIGATOR
References: