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HIV Fat Redistribution and the Evaluation of Brown Fat

9 août 2021 mis à jour par: Steven K. Grinspoon, MD, Massachusetts General Hospital

FDG/PET Imaging for the Assessment of Brown Adipose Tissue in HIV Lipodystrophy

The specific aims of this study are to determine whether HIV-infected patients with significant fat redistribution and ectopic fat accumulation have increased brown adipose tissue using 18F-FDG Positron Emission Tomography techniques.

Recent studies suggest down regulation of Dicer, a major component of miRNA has an important role in the differentiation and function of brown and white adipose tissue and may contribute to lipodystrophy. Therefore we will expand on recent research in this area by recruiting HIV-infected men with lipodystrophy. We will perform subcutaneous fat biopsies of the dorsocervical and abdominal fat in a subset of HIV-infected and non-HIV-infected men in order to explore further the question of down regulation of Dicer and its implication on metabolic abnormalities in this population.

Aperçu de l'étude

Statut

Complété

Les conditions

Description détaillée

Among individuals infected with HIV, highly active antiretroviral therapy has reduced the incidence of morbidity and mortality however, despite recent improvements in newer antiretrovirals patients continue to exhibit secondary effects related to body composition such as lipoatrophy of the periphery, increased adiposity of the trunk and lipomatosis, especially of the dorsocervical spine. Changes in body composition have been reported in 40-50% of HIV-infected patients. Several studies have shown that antiretroviral therapy contributes to changes in body composition and is coupled with increased dyslipidemia, insulin resistance and diabetes.

Accumulation of fat over the dorsocervical spine, or "buffalo" has been reported in 2% to 13% of HIV-infected patients. Enlargement of adipose tissue in the dorsocervical region involves subcutaneous fat and is therefore unique to fat accumulation of the abdominal area. Guallar et al. examined dorsocervical adipose tissue after surgical removal and found that adipose tissue in this area showed substantial levels of the marker gene of brown fat, uncoupling protein 1 (UCP-1) suggesting there may be brown adipose tissue (BAT) in HIV infected individuals with lipomatosis of the dorsocervical spine. Until recently, BAT was known to be present in rodents throughout their lifetime and was thought to be present in humans only during infancy and early childhood. However, recent studies using 18F-FDG PET-CT have confirmed the presence of BAT in adults. Brown adipose tissue is known to affect whole-body metabolism and may be related to insulin sensitivity as well as susceptibility to weight gain.

Using 18F-FDG PET techniques, our group has evaluated HIV-infected subjects with lipoatrophy and noted there was significantly increased glucose uptake into subcutaneous tissue which may suggest presence of BAT in HIV-infected patients. However our previous study did not specifically examine areas of BAT in the subjects. Therefore, using 18F-FDG PET-CT in addition to fat biopsies we propose to explore the presence of BAT in fat depots among HIV-infected patients with fat redistribution, focusing specifically in the cervical area.

Also, as recent studies suggest down regulation of Dicer, a major component of miRNA has an important role in the differentiation and function of brown and white adipose tissue and may contribute to lipodystrophy. We will perform subcutaneous fat biopsies of the dorsocervical and abdominal fat in a subset of HIV-infected and non-HIV-infected men in order to explore further the question of down regulation of Dicer and its implication on metabolic abnormalities in this population.

Type d'étude

Observationnel

Inscription (Réel)

27

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • États-Unis
    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02114
        • Massachusetts General Hospital

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

20 ans à 60 ans (Adulte)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Homme

Méthode d'échantillonnage

Échantillon non probabiliste

Population étudiée

HIV infected patients with fat redistribution and non HIV controls

La description

Subject Selection and Enrollment:

Twenty male subjects comprised of four distinct groups will be recruited for the study. Subjects will be matched by age and body-mass index. The four groups are:

Group 1: HIV infected with fat redistribution (lipohypertrophy) (n=5) Group 2: HIV infected with fat redistribution (lipoatrophy) (n=5) Group 3: Healthy Controls (n=10)

Inclusion Criteria for HIV+ with fat redistribution (lipohypertrophy) subjects (Group 1)

  1. Evidence of HIV infection
  2. Age ≥ 20 and ≤ 60 years of age
  3. BMI measurement between 25-29.9 kg/m2
  4. HIV positive, on a stable HAART treatment regimen (including an NRTI) for > 12 months
  5. Evidence of significant fat redistribution rated by the investigator, including 1) significant fat atrophy of the face, arms or legs, and 2) significant increase in fat accumulation of the neck.

Exclusion Criteria for HIV+ with fat redistribution (lipohypertrophy) (Group 1)

  1. Hemoglobin < 10.0 g/dL
  2. Diabetes or on medications for diabetes
  3. Abnormal thyroid function
  4. Therapy with medications such as beta blockers, alpha-blockers, sympatholytic drugs
  5. Chronic adrenergic drug use (>3 months) and benzodiazepine use.
  6. Therapy with glucocorticoids (oral and inhaled), growth hormone or other anabolic agents currently or within the past 3 months
  7. Current substance abuse, including alcohol, cocaine and/or heroin
  8. Other serious or chronic diseases
  9. New antiretroviral regimen in the past 12 months
  10. Any new serious opportunistic infection within the past 6 weeks

Inclusion Criteria for HIV+ with fat redistribution (lipoatrophy) (Group 2)

  1. Evidence of HIV infection
  2. Age ≥ 20 and ≤ 60 years of age
  3. BMI measurement between 18-24 kg/m2
  4. HIV positive, on a stable HAART treatment regimen (including an NRTI) for > 12 months
  5. No evidence of fat redistribution rated by the investigator.

Exclusion Criteria for HIV+ with fat redistribution (lipoatrophy) (Group 2)

  1. Hemoglobin < 10.0 g/dL
  2. Diabetes or on medications for diabetes
  3. Abnormal thyroid function
  4. Therapy with medications such as beta blockers, alpha-blockers, sympatholytic drugs
  5. Chronic adrenergic drug use (>3 months) and benzodiazepine use.
  6. Therapy with glucocorticoids (oral and inhaled), growth hormone or other anabolic agents currently or within the past 3 months
  7. Current substance abuse, including alcohol, cocaine and/or heroin
  8. Other serious or chronic diseases
  9. New antiretroviral regimen in the past 12 months
  10. Any new serious opportunistic infection within the past 6 weeks

Inclusion Criteria for Healthy Controls (Group 3)

  1. No history of HIV infection
  2. Age ≥ 20 and ≤ 60 years of age
  3. BMI measurement between 18-29.9 kg/m2

Exclusion Criteria for Healthy Controls (Group 3)

  1. Hemoglobin <10.0 g/dL.
  2. Diabetes or on medications for diabetes
  3. Abnormal thyroid function.
  4. Therapy with medications such as beta blockers, alpha-blockers, sympatholytic drugs
  5. Chronic adrenergic drug use (>3 months) and benzodiazepine use.
  6. Therapy with glucocorticoid (oral and inhaled), growth hormone or other anabolic agents currently or within the past 3 months
  7. Current substance abuse, including alcohol, cocaine and/or heroin
  8. Any history of serious or chronic diseases -

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

Cohortes et interventions

Groupe / Cohorte
HIV-infection with fat redistribution (lipoatrophy)
  1. Evidence of HIV infection
  2. Age ≥ 20 and ≤ 60 years of age
  3. BMI measurement between 18-24 kg/m2
  4. HIV positive, on a stable HAART treatment regimen (including an NRTI) for > 12 months
  5. No evidence of fat redistribution rated by the investigator.
Healthy controls
  1. No history of HIV infection
  2. Age ≥ 20 and ≤ 60 years of age
  3. BMI measurement between 18-29.9 kg/m2
HIV-infected with fat redistribution (lipohypertrophy)
  1. Evidence of HIV infection
  2. Age ≥ 20 and ≤ 60 years of age
  3. BMI measurement between 25-29.9 kg/m2
  4. HIV positive, on a stable HAART treatment regimen (including an NRTI) for > 12 months
  5. Evidence of significant fat redistribution rated by the investigator, including 1) significant fat atrophy of the face, arms or legs, and 2) significant increase in fat accumulation of the neck.
Dicer Cohort
30 men [HV-infected with fat redistribution (n = 10), HIV-infected without fat redistribution (n=10), and healthy controls (n= 10)] will be recruited for this group.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Brown Fat
Délai: Baseline
Brown Fat will be assessed by PET FDG
Baseline

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
UCP-1
Délai: Baseline
UCP-1 will be analyzed from tissue collected from a fat biopsy of dorsocervical spine fat accumulation.
Baseline
Indirect Calorimetry
Délai: Baseline
Indirect Calorimetry will be performed to measure resting energy expenditure
Baseline
Anthropometrics
Délai: Baseline
Anthropometric measurements of waist to hip ratio, leg circumference, arm circumference and neck circumference will be performed using a standardized technique.
Baseline
Glucose tolerance
Délai: Baseline
A baseline glucose level will be obtained and then patients will consume a 75g glucose beverage. Subjects must complete the beverage within 5-10 minutes. Subsequently, blood glucose at +30, +60, +90, and +120 minutes, insulin levels will be assessed at baseline and +120 minutes. Glucose tolerance will be calculated by insulin area under the curve in response to OGTT.
Baseline
miRNAs
Délai: Baseline
A baseline miRNA profile will be assessed and subsequent pathways
Baseline

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Massachusetts General Hospital

Collaborateurs

Beth Israel Deaconess Medical Center

Les enquêteurs

  • Directeur d'études: Martin Torriani, MD, Massachusetts General Hopsital

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 mars 2010

Achèvement primaire (Réel)

1 juin 2014

Achèvement de l'étude (Réel)

1 août 2015

Dates d'inscription aux études

Première soumission

25 mars 2010

Première soumission répondant aux critères de contrôle qualité

1 avril 2010

Première publication (Estimation)

2 avril 2010

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

16 août 2021

Dernière mise à jour soumise répondant aux critères de contrôle qualité

9 août 2021

Dernière vérification

1 août 2021

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 2009P-001836

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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