Clinical trial NCT06889142: Impact of NMN Supplementation on CD4+ T Cell Recovery in HIV Patients With Immunological Failure
Official title: Proof-of-Concept Study: Investigating the Impact of NMN Supplementation on CD4+ T Cell Recovery in Virologically Suppressed HIV Patients With Immunological Failure
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Human Immunodeficiency Virus
Keywords: HIV
immunologic failure
proof of concept
CD4+ T cell recovery
immunological non-responders
Nicotinamide Mononucleotide
Lead sponsor: TriHealth Inc.
Sponsor class: OTHER
Collaborators: name: DoNotAge.org
First posted: 2025-03-21
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: proof of concept
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Primary Outcome
timeFrame: 12 weeks
Secondary outcomes:
measure: CD38
timeFrame: collected at baseline visit followed by monthly collections for total of 3 months
measure: HLA-DR expression
timeFrame: collected at baseline visit followed by monthly collections for total of 3 months
measure: TNF-alpha
timeFrame: collected at baseline visit followed by monthly collections for total of 3 months
measure: NAD(+) levels
timeFrame: collected at baseline visit followed by monthly collections for total of 3 months
measure: IL-6
timeFrame: collected at baseline visit followed by monthly collections for total of 3 months
measure: HS-CRP
timeFrame: collected at baseline visit followed by monthly collections for total of 3 months
measure: Changes on Quality-of-life Questionnaire (QOL): WHO QOL HIV BREF
timeFrame: collected at baseline visit followed by monthly collections for total of 3 months
Other outcomes:
Locations:
Study officials:
affiliation: TriHealth Inc.
name: Madelyn Mirande, DO
role: STUDY_CHAIR
References:
citation: 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 Malformations, and Niacin Supplementation. N Engl J Med. 2017 Aug 10;377(6):544-552. doi: 10.1056/NEJMoa1616361.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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).
citation: 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.
citation: 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.
citation: Dessie G, Mulugeta H, Wagnew F, Zegeye A, Kiross D, Negesse A, Aynalem YA, Getaneh T, Ohringer A, Burrowes S. Immunological Treatment Failure Among Adult Patients Receiving Highly Active Antiretroviral Therapy in East Africa: A Systematic Review and Meta-Analysis. Curr Ther Res Clin Exp. 2021 Jan 5;94:100621. doi: 10.1016/j.curtheres.2020.100621. eCollection 2021.
citation: Carvalho-Silva WHV, Andrade-Santos JL, Souto FO, Coelho AVC, Crovella S, Guimaraes RL. Immunological recovery failure in cART-treated HIV-positive patients is associated with reduced thymic output and RTE CD4+ T cell death by pyroptosis. J Leukoc Biol. 2020 Jan;107(1):85-94. doi: 10.1002/JLB.4A0919-235R. Epub 2019 Nov 5.
citation: Burnie J, Fernandes C, Chaphekar D, Wei D, Ahmed S, Persaud AT, Khader N, Cicala C, Arthos J, Tang VA, Guzzo C. Identification of CD38, CD97, and CD278 on the HIV surface using a novel flow virometry screening assay. Sci Rep. 2023 Dec 27;13(1):23025. doi: 10.1038/s41598-023-50365-0.
citation: Bono V, Augello M, Tincati C, Marchetti G. Failure of CD4+ T-cell Recovery upon Virally-Effective cART: an Enduring Gap in the Understanding of HIV+ Immunological non-Responders. New Microbiol. 2022 Jul;45(3):155-172.