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Use of Labeled Glucose to Study Lymphocyte Replication and Survival in HIV-Infected Patients

Studies of Lymphocyte Kinetics Using Stable Isotopes

This study will examine how quickly white blood cells called CD4 lymphocytes replicate (divide) and how long they live in both HIV-infected and non-infected people by measuring how quickly the genetic material (DNA) of cells is replicated. To do this, participants will receive infusions of glucose, a non-radioactive form of a type of sugar. Cells normally use glucose to make various products needed for cell growth and replication, including cell DNA. Measuring how much glucose cells incorporate into their DNA can provide important information about cell replication. This rate of incorporation will be examined and compared in HIV-infected people and in healthy, normal volunteers.

HIV-infected patients and non-infected healthy volunteers 18 years of age and older may be eligible for this study. Candidates will be screened with a medical history, physical examination, chest X-ray, electrocardiogram (EKG) and blood tests.

Participants will be given a continuous infusion of glucose at a dose of up to 60 grams (about 2 ounces) per day for up to 5 days. The glucose will be delivered through a catheter (thin plastic tube) placed in an arm vein. Blood samples will be collected as often as daily in the first week following the infusion and then from twice a week to once a month for up to 4 years. Alternatively, patients may undergo leukapheresis a procedure for collecting quantities of lymphocytes up to 10 times during the first month after the infusion, and possibly later as well, but no more often than once every 2 weeks. For this procedure, whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are removed and the rest of the blood is returned to the body either through the same needle or through a second needle in the other arm. Participants may be asked to receive up to four glucose infusions. There will be at least a 2-week interval between infusions. Participants who have more than three leukapheresis procedures within 3 weeks will have at least 6 weeks between infusions.

Participants will be followed periodically in the outpatient clinic for evaluation and tests.

This study may provide a better understanding of how HIV causes disease and progressive weakening of the immune system and how therapies affect immunity.

Aperçu de l'étude

Statut

Résilié

Intervention / Traitement

Description détaillée

Understanding the rate of lymphocyte replication and destruction in HIV-infected patients, as well as the effects of therapy on lymphocyte replication should lead to a better understanding of the mechanisms behind the immunodeficiency induced by HIV. To examine this directly, up to 100 HIV-infected patients will receive up to 5 days of continuous infusions with [6,6-(2)H(2)]-glucose, a nonradioactive, stable isotope of glucose that is safe to administer. The deuterium is incorporated into DNA via metabolism of glucose to ribose and incorporation into nucleotides. The rate of incorporation can be measured in subpopulations of cells to determine the rate of replication of those cells. Fifty HIV-uninfected persons will also be enrolled in the protocol to allow a determination of lymphocyte kinetics in individuals with normally functioning immune systems or immune systems that may have been affected by other diseases. All participants in this study will be reimbursed for the inconvenience and discomfort associated with study participation.

Type d'étude

Interventionnel

Inscription (Réel)

54

Phase

  • N'est pas applicable

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

    • Maryland
      • Bethesda, Maryland, États-Unis, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

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

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Tout

La description

  • INCLUSION CRITERIA:

FOR PATIENTS:

18 years or older.

Able to provide informed consent and willing to comply with study requirements and clinic policies.

Negative urine pregnancy test (for women of childbearing potential).

Hemoglobin greater than 10 mg/dl.

Adequate venous access in the arms for blood drawing and 5 day infusions, and lymphapheresis

Willingness to allow stored samples to be used for future studies of HIV infection and/or immunological function, and willingness to have HLA typing performed. (For previously enrolled patients, patients would be requested, but not required, to provide permission to use stored samples in the future, and to permit HLA testing

FOR HIV POSITIVE PATIENTS:

Documented HIV infection (ELISA/Western blot positive or, for acute seroconverters, PCR positive).

FOR HIV NEGATIVE PATIENTS:

Negative ELISA/Western blot.

EXCLUSION CRITERIA:

Diabetes mellitus requiring drug therapy.

Active substance abuse or prior history of substance abuse which may interfere with protocol compliance.

Psychiatric illness or disturbance which, in the assessment of the protocol team, may affect patient safety or compliance.

Significant underlying cardiac, pulmonary, renal, gastrointestinal, rheumatologic or CNS disease as detectable on routine history, physical exam, or screening laboratory studies. Patients would be excluded if they had an acute or chronic underlying medical problem that in the judgment of the principal investigator could be exacerbated by participating in the protocol or that would make it difficult for them to comply with the protocol requirements.

Pregnancy or breast-feeding.

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

  • Objectif principal: Science basique
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: HIV-infected subjects
HIV-infected adults
[6,6-2H2]-glucose will be administered as a continuous IV infusion for one to five days.
Expérimental: HIV-negative subjects
HIV-negative adults
[6,6-2H2]-glucose will be administered as a continuous IV infusion for one to five days.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Kinetics of lymphocyte turnover
Délai: Day 2, 5 (end of [6,6-2H2]-glucose infusion), 6, 8, 12, 16, 20, and 28. After day 28, visits will occur monthly through 6 months, then no more often than every 3 months through 2 years.
Cell turnover markers
Day 2, 5 (end of [6,6-2H2]-glucose infusion), 6, 8, 12, 16, 20, and 28. After day 28, visits will occur monthly through 6 months, then no more often than every 3 months through 2 years.

Collaborateurs et enquêteurs

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

Les enquêteurs

  • Chercheur principal: Joseph A Kovacs, M.D., National Institutes of Health Clinical Center (CC)

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.

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 (Réel)

25 février 1998

Achèvement primaire (Réel)

1 janvier 2020

Achèvement de l'étude (Réel)

29 mai 2020

Dates d'inscription aux études

Première soumission

3 novembre 1999

Première soumission répondant aux critères de contrôle qualité

3 novembre 1999

Première publication (Estimation)

4 novembre 1999

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

1 juin 2020

Dernière mise à jour soumise répondant aux critères de contrôle qualité

29 mai 2020

Dernière vérification

1 mai 2020

Plus d'information

Termes liés à cette étude

Autres numéros d'identification d'étude

  • 970191
  • 97-I-0191

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

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 .

Essais cliniques sur VIH

Essais cliniques sur [6,6-2H2]-glucose

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