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- Ensaio Clínico NCT01093651
Dipeptidyl Peptidase-4 Inhibition and Immune Function in HIV (DPPIVinHIV)
22 de janeiro de 2014 atualizado por: Kevin Yarasheski, PhD, Washington University School of Medicine
A Blinded Randomized Controlled Pilot Immunologic and Virologic Safety Trial of an FDA-approved DPPIV-inhibitor in HIV+ Men and Women
We will test the safety of a new class of anti-diabetes compounds (DPPIV-inhibitors) in people living with HIV.
Future trials will examine efficacy for treating diabetes and reducing cardiovascular disease risk in people living with HIV.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
Human immunodeficiency virus (HIV)-infection and treatment with antiretroviral therapies are associated with several cardiometabolic risk factors; insulin resistance, diabetes, dyslipidemia, central adiposity, that increase risk for MI and stroke.
A new class of drugs used to treat type 2 diabetes has been introduced; Dipeptidyl peptidase-IV (DPPIV)-inhibitors (Januvia®, Onglyza®, alogliptin).
Dipeptidyl peptidase-IV (DPPIV)-inhibition could be a safe and effective therapy for HIV-associated insulin resistance and diabetes.
However, no safety data exist.
The research question is: If HIV+ adults with stable immunologic (CD4+ T-cell count >350 cells/μL) and virologic (plasma HIV RNA <50 copies/mL) function are given a DPPIV-inhibitor would their CD4+ T-cell count and plasma HIV RNA level increase, decrease, or stay the same?
Theoretically, DPPIV-inhibition could enhance their immune system by increasing SDF-1α levels; a potent inhibitor of HIV-entry into T-cells, or harm the HIV+ immune system by inactivating CD26 on immune cells.
We hypothesize that DPPIV-inhibition will not harm the immune system in HIV+ people.
We propose a blinded randomized controlled pilot safety trial of an FDA-approved DPPIV-inhibitor in virologically- and immunologically-stable HIV+ men and women.
We will monitor CD4+ T-cell count, plasma HIV RNA levels, immune activation markers, and safety outcomes (lipid/lipoprotein profiles, blood pressure, kidney and liver function) during 4-6 months of DPPIV-inhibitor exposure vs placebo in 20 HIV+ adults.
If safety is confirmed, the efficacy of DPPIV-inhibition in HIV+ with insulin resistance will be tested in future trials that examine potential glucoregulatory and cardiovascular benefits.
Tipo de estudo
Intervencional
Inscrição (Real)
20
Estágio
- Fase 2
- Fase 3
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Missouri
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Saint Louis, Missouri, Estados Unidos, 63110
- Washington University School of Medicine
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos a 65 anos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Thirty 18-65 yr old HIV-infected men and women (with source documentation of HIV status) who are stable on any antiretroviral therapy (cART) regimen
- Have stable (at least the past 12-months) immunologic (>350 CD4+ T-cells/µL) and virologic (<50 copies HIV RNA/mL) status.
- BMI 18-42kg/m2;
- Normal blood chemistry for at least 1 month prior to enrollment;
- Platelet count > 30,000/mm3, absolute neutrophil count >750/mm3, transaminases < 2.5x the upper limit of normal (ULN).
- Long-term non-progressors (not on ART) are not eligible.
Exclusion Criteria:
- CD4+ T-cell count <350 cells/µL or detectable plasma HIV RNA (>50 copies HIV RNA/mL) within the past 12-months. During the study, if CD4+ T-cell count declines by >100 cells/µL, or if plasma HIV RNA becomes detectable (>50 copies HIV RNA/mL after repeat analysis 2wks apart), and the participant denies any lapse in their anti-HIV medication regimen, the study medication will be stopped and an adverse event documented. If at any time during the study, two participants experience a reduction in T-cell count >100 cells/µL, or their plasma HIV RNA levels become detectable (>50 copies HIV RNA/mL after repeat analysis 2wks apart), and they are confirmed (by unblinding) to have received sitagliptin, the study will be stopped for serious safety concerns.
- Systemic, secondary or opportunistic infection within past 12-months.
- Fasting glucose intolerance (FBG >100mg/dL), fasting hyperinsulinemia (>15µU/mL), or fasting insulin resistance (Homeostasis model for insulin resistance (HOMA) >3.0). Any agents that might alter glucose metabolism (insulin, TZDs, metformin, glucocorticoids, sulfonylurea, corticosteroids, megace, rhGH, GH-secretagogue) during the 3 months prior to enrollment or at any time during enrollment. Volunteers with T2DM, IDDM or diabetic ketoacidosis will not be enrolled.
- History of serious CV disease or NYHA Functional Class III or IV, (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, valve disease (murmur), stroke, uncontrolled high blood pressure (resting >160/95 mmHg), irregular heart rhythm, resting ST-segment depression >1mm). Treatment with medications for a CV condition (cardiac glycosides α- or ß-blockers). Some antihypertensive medications (calcium-channel blocker, diuretic, angiotensin II receptor blockers (ARB), angiotensin converting enzyme inhibitors (ACE)) will be permitted.
- Moderate to severe renal insufficiency. Serum creatinine >1.7 mg/dL (men) >1.5 mg/dL (women).
- Known allergy or hypersensitivity to DPPIV-inhibitors.
- Plan to change anti-HIV medication regimen or prophylaxis for opportunistic infection within 6-months of starting study.Transitions among efavirenz-based regimens will be allowed (e.g., Efavirenz + lamivudine + zidovudine (combivir) to Efavirenz + emtricitabine + tenofovir (Atripla)).
- Lipid-lowering medications are permitted (fibrate or statin or niacin), but must be stable on that agent for at least 3 months prior to enrollment. Lipid-lowering agents cannot be started during the treatment period.
- Chronic hepatitis B infection (HB surface antigen positive). Active hepatitis C infection (detectable Hep C RNA). Those who have cleared hepatitis B or C infection are eligible.
- Hematocrit <34% in men or <25% in women with symptoms (fatigue, "tired-legs", shortness of breath). Hemoglobin <10 gm/100ml with symptoms.
- Nausea, vomiting, diarrhea (>4 loose stools/day) that are unresponsive to treatment. History of eating disorder or significant GI-disease.
- Pregnant or nursing mothers. Women must agree to use an acceptable form of birth control during the study. If birth control pills are used, the woman must be stable on these medications for at least 6 months prior to enrollment.
- Active malignancy or treatment with chemotherapeutic agents or radiation therapy (within past 12 months).
- >10% unintentional body weight loss during the 12 months prior to enrollment.
- "Blinded" investigational drugs/medications during the 3 months prior to enrollment that will not be unblinded before enrollment. Open-label investigational drugs are permitted (within past 3 months, no plan to stop during enrollment and not known to affect glucose, lipid, adipose tissue or liver metabolism).
- Over the counter agents that might alter glucose, lipid, or adipose tissue metabolism (e.g., creatine monohydrate, chromium picolinate, amino acid/protein supplements, medium- or long-chain fatty acids) within 1 month of enrollment. These supplements are not permitted during the treatment period.
- Reduced cognitive function/unable to provide voluntary informed consent. Prisoners are excluded.
- Active substance abuse that the physician-scientist believes may compromise safety, compliance, or interfere with study drug or data interpretation.
- Any cytokine or anti-cytokine therapy during 3 months prior to enrollment.
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: DPPIV inhibition
Four to six months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status.
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100 mg sitagliptin daily for 4-6 months
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Comparador de Placebo: Placebo
Four to six months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status.
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Daily placebo for 4-6 months
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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CD4+ T-cell Count
Prazo: Monthly for 4 months
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Monthly for 4 months
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Plasma HIV Viremia (Viral Load)
Prazo: Monthly for 6 months
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Percentage of participants with plasma HIV RNA copy number less than 48 copies/mL
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Monthly for 6 months
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Soluble TNFR2; Serum Biomarkers of Immune Activation
Prazo: Baseline, week 8, week 16
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serum soluble tumor necrosis factor receptor-2 concentration
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Baseline, week 8, week 16
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SDF1α; Serum Biomarkers of Immune Activation
Prazo: Baseline, week 8, week 16
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serum stromal cell-derived factor-1α concentration
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Baseline, week 8, week 16
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RANTES; Serum Biomarkers of Immune Activation
Prazo: Baseline, week 8, week 16
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serum Regulated on Activation, Normal T cell Expressed and Secreted concentration
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Baseline, week 8, week 16
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Oral Glucose Tolerance
Prazo: Baseline, week 8, week 16
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Area under the 75-gr oral glucose tolerance curve (AUCg) based on plasma glucose values measured at 0, 30, 60, 90, and 120 mins post-glucose challenge.
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Baseline, week 8, week 16
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Self-reported Symptoms
Prazo: Monthly for 4 months
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Cumulative number of self-reported symptoms based on the Division of AIDS Grading Scale for the Severity of Adult Adverse Events (0-4 scale where 0 is no new symptoms, 4 is serious adverse event or toxicity)
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Monthly for 4 months
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Kevin E Yarasheski, PhD, Washington University School of Medicine
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de junho de 2010
Conclusão Primária (Real)
1 de junho de 2011
Conclusão do estudo (Real)
1 de junho de 2012
Datas de inscrição no estudo
Enviado pela primeira vez
23 de março de 2010
Enviado pela primeira vez que atendeu aos critérios de CQ
24 de março de 2010
Primeira postagem (Estimativa)
26 de março de 2010
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
17 de fevereiro de 2014
Última atualização enviada que atendeu aos critérios de controle de qualidade
22 de janeiro de 2014
Última verificação
1 de janeiro de 2014
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Distúrbios do Metabolismo da Glicose
- Doenças Metabólicas
- Hiperinsulinismo
- Resistência a insulina
- Hipoglicemiantes
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Hormônios
- Hormônios, Substitutos Hormonais e Antagonistas Hormonais
- Inibidores de Protease
- Incretinas
- Inibidores de Dipeptidil-Peptidase IV
- Fosfato de Sitagliptina
Outros números de identificação do estudo
- KEY03222010
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .
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