Impact of NMN Supplementation on CD4+ T Cell Recovery in HIV Patients With Immunological Failure

Официальное название

Proof-of-Concept Study: Investigating the Impact of NMN Supplementation on CD4+ T Cell Recovery in Virologically Suppressed HIV Patients With Immunological Failure

Обзор

This proof-of-concept study aims to investigate the potential impact of supplementing with Nicotinamide Mononucleotide (NMN), a direct precursor of NAD+ on CD4+ T cell recovery in virologically suppressed HIV patients experiencing immunological failure on ART. We hypothesize that NMN supplementation will increase intracellular NAD+ levels, thereby improving CD4+ T cell function and potentially reversing immunological failure. A small cohort of patients will be recruited to evaluate the primary outcome of change in CD4+ T cell count from baseline to the end of the study period after receiving NMN daily for 12 weeks. Secondary outcomes including safety and tolerability, impact on pro-inflammatory markers, increase in NAD+ levels, immune activation markers and change in quality of life questionnaire scores. Patients will participate in two in person visits including a baseline and end of study with two telephone encounters. Patients will take 1,000mg NMN daily for a total of 12 weeks during which they will keep a daily log of doses taken and any side effects experienced. At all visits labs and quality of life questionnaire will be completed with complete physical exam to be done at baseline and end of study visit.

Вмешательства

• Пищевая добавка Nicotinamide Mononucleotide
  The dietary supplement NMN \[1,000mg\] will be taken orally by participants daily for a total of 12 weeks

Первичные конечные точки

• Primary Outcome [Срок оценки: 12 weeks]

Вторичные конечные точки (7)

• CD38 [Срок оценки: collected at baseline visit followed by monthly collections for total of 3 months]
• HLA-DR expression [Срок оценки: collected at baseline visit followed by monthly collections for total of 3 months]
• TNF-alpha [Срок оценки: collected at baseline visit followed by monthly collections for total of 3 months]
• NAD(+) levels [Срок оценки: collected at baseline visit followed by monthly collections for total of 3 months]
• IL-6 [Срок оценки: collected at baseline visit followed by monthly collections for total of 3 months]
• HS-CRP [Срок оценки: collected at baseline visit followed by monthly collections for total of 3 months]
• Changes on Quality-of-life Questionnaire (QOL): WHO QOL HIV BREF [Срок оценки: collected at baseline visit followed by monthly collections for total of 3 months]

Критерии участия

Критерии включения

• HIV-infected adults aged 18 years or older
• Virologically suppressed on ART documented with two negative viral loads separated by at least 6 months
• Confirmed diagnosis of immunological failure (CD4+ T cell count <350 cells/µL 2 years after effective ART initiation)
• Willing to provide informed consent

Критерии исключения

• Active opportunistic infections
• Known allergies or sensitivities to NMN or any components of the NMN supplement
• Current or recent use of other supplements or medications known to affect NAD+ metabolism (Niacin, NR, NMNH, etc.)
• Pregnancy or breastfeeding
• Significant liver or kidney disease
• Active malignancy
• History of uncontrolled substance abuse
• Severe medical conditions that might interfere with study participation
• Unable to consent

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Shi H, Enriquez A, Rapadas M, Martin EMMA, Wang R, Moreau J, Lim CK, Szot JO, Ip E, Hughes JN, Sugimoto K, Humphreys DT, McInerney-Leo AM, Leo PJ, Maghzal GJ, Halliday J, Smith J, Colley A, Mark PR, Collins F, Sillence DO, Winlaw DS, Ho JWK, Guillemin GJ, Brown MA, Kikuchi K, Thomas PQ, Stocker R, Giannoulatou E, Chapman G, Duncan EL, Sparrow DB, Dunwoodie SL. NAD Deficiency, Congenital Malformati PMID 28792876
• Braidy N, Berg J, Clement J, Khorshidi F, Poljak A, Jayasena T, Grant R, Sachdev P. Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes. Antioxid Redox Signal. 2019 Jan 10;30(2):251-294. doi: 10.1089/ars.2017.7269. Epub 2018 May 11. PMID 29634344
• Song Q, Zhou X, Xu K, Liu S, Zhu X, Yang J. The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update. Adv Nutr. 2023 Nov;14(6):1416-1435. doi: 10.1016/j.advnut.2023.08.008. Epub 2023 Aug 22. PMID 37619764
• Lebouche B, Jenabian MA, Singer J, Graziani GM, Engler K, Trottier B, Thomas R, Brouillette MJ, Routy JP. The role of extended-release niacin on immune activation and neurocognition in HIV-infected patients treated with antiretroviral therapy - CTN PT006: study protocol for a randomized controlled trial. Trials. 2014 Oct 7;15:390. doi: 10.1186/1745-6215-15-390. PMID 25293882
• Mo Y, Yue M, Yim LY, Zhou R, Yu C, Peng Q, Zhou Y, Luk TY, Lui GC, Huang H, Lim CYH, Wang H, Liu L, Sun H, Wang J, Song Y, Chen Z. Nicotinamide mononucleotide impacts HIV-1 infection by modulating immune activation in T lymphocytes and humanized mice. EBioMedicine. 2023 Dec;98:104877. doi: 10.1016/j.ebiom.2023.104877. Epub 2023 Nov 17. PMID 37980794
• MD MG. Unveiling the Nexus of CD38 Overactivation, NAD+ Depletion, and Mitochondrial Dysfunction in Immunological Failure Among Virologically Suppressed HIV Patients. 2024(https://nortonhealthcaremedicaljournal.scholasticahq.com/article/118564-unveiling-the-nexus-of-cd38-overactivation-nad-depletion-and-mitochondrial-dysfunction-in-immunological-failure-among-virologically-suppressed-hiv).
• Zhu A, Real F, Zhu J, Greffe S, de Truchis P, Rouveix E, Bomsel M, Capron C. HIV-Sheltering Platelets From Immunological Non-Responders Induce a Dysfunctional Glycolytic CD4+ T-Cell Profile. Front Immunol. 2022 Feb 11;12:781923. doi: 10.3389/fimmu.2021.781923. eCollection 2021. PMID 35222352
• Fan L, Li P, Yu A, Liu D, Wang Z, Wu Y, Zhang D, Zou M, Ma P. Prevalence of and prognosis for poor immunological recovery by virally suppressed and aged HIV-infected patients. Front Med (Lausanne). 2023 Oct 19;10:1259871. doi: 10.3389/fmed.2023.1259871. eCollection 2023. PMID 37928477

Идентификаторы

NCT: NCT06889142 · 24-089

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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