Facial Lipoatrophy Trial: Immediate Versus Deferred Injections of Poly-L-Lactic Acid for HIV Facial Lipoatrophy

HIV Infections Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00126308
• Other study ID #: V1-0 4-05
• Secondary ID: ACTR012605000132
• Status: Terminated
• Phase: Phase 4
• First received: August 1, 2005
• Last updated: March 31, 2009
• Start date: November 2005
• Est. completion date: May 2007

Study information

• Verified date: March 2009
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 100
• Est. completion date: May 2007
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• HIV-Associated Lipodystrophy
• HIV-Associated Lipodystrophy Syndrome
• Lipodystrophy

Intervention

Device:
• poly-L-lactic acid
immediate injections poly-L-lactic acid (4 bilateral treatments - 8 vials)
• poly-L-lactic acid
delayed (24 weeks) poly-L-lactic acid injections (4 bilateral treatment - 8 vials)

Locations

Country	Name	City	State
Australia	The Care and Prevention Programme - Adelaide University	Adelaide	South Australia
Australia	Gladstone Road Medical Centre	Brisbane	Queensland
Australia	Queensland Health - AIDS Medical Unit	Brisbane	Queensland
Australia	Dr Doong's Surgery	Burwood	New South Wales
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Gold Coast Sexual Health Clinic	Gold Coast	Queensland
Australia	Clinic 87	Nambour	Queensland
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	407 Doctors	Sydney	New South Wales
Australia	AIDS Research Initiative	Sydney	New South Wales
Australia	Albion Street Clinic	Sydney	New South Wales
Australia	Holdsworth House General Practice	Sydney	New South Wales
Australia	Liverpool Health Service	Sydney	New South Wales
Australia	Royal North Shore Hospital	Sydney	New South Wales
Australia	St. Vincent's Hospital	Sydney	New South Wales
Australia	Taylor Square Private Clinic	Sydney	New South Wales
Australia	Waratah Clinic, St. George Hospital	Sydney	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales

Sponsors (9)

Lead Sponsor	Collaborator
Kirby Institute	Abbott, AIDS Council of New South Wales, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Hoffmann-La Roche, Merck Sharp & Dohme Corp., The University of New South Wales

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint at 24 weeks will be change from baseline in facial soft tissue volume as measured by spiral computed tomography (CT).		24 weeks	No
Secondary	Change from baseline at week 96 in facial soft tissue volume as measured by spiral CT scan		96 weeks	No
Secondary	Change from baseline at weeks 24 and 96 in physician and patient assessment of facial lipoatrophy severity		24 and 96 weeks	No
Secondary	Change from baseline at weeks 24 and 96 in peripheral fat as assessed by dual-energy X-ray absorptiometry (DEXA)		24 and 96 weeks	No
Secondary	Change from baseline at weeks 24 and 96 in quality of life		24 and 96 weeks	No
Secondary	Change from baseline at weeks 24 and 96 in antiretroviral therapy (ART) adherence and plasma HIV-RNA		24 and 96 weeks	No
Secondary	All serious, grade 3 or 4 clinical adverse events and any adverse event leading to change/s in ART or discontinuation of PLA		24 and 96 weeks	Yes
Secondary	All serious, grade 3 or 4 clinical adverse events (AEs) and any event leading to change/s in ART reported to week 96		96 weeks	Yes
Secondary	All AEs attributable to study treatment reported to week 96		week 96	Yes

External Links

•   NCHECR Website (Australia)