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| Name | Class |
|---|---|
| DoNotAge.org | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment with 1,000mg Nicotinamide Mononucleotide daily | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nicotinamide Mononucleotide | Dietary Supplement | The dietary supplement NMN [1,000mg] will be taken orally by participants daily for a total of 12 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Primary Outcome | The primary outcome of this study will be the change in CD4+ T cell count from baseline to the end of the study period. [normal range: 500-1500 cells/mm^3; improved outcomes with increase to normal range] | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| CD38 | Changes in immune activation markers - CD38 expression [healthy individuals expression on T cell <10-20%, untreated HIV elevated >60-90%, HIV on ART ~ 20-30%; low percentage correlates with improved immune function] | collected at baseline visit followed by monthly collections for total of 3 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Martin L. Gnoni, MD | Contact | 513-568-7462 | martin_gnoni@trihealth.com | |
| Madelyn Mirande, DO | Contact | 715-307-1273 | madelyn_mirande@trihealth.com |
| Name | Affiliation | Role |
|---|---|---|
| Madelyn Mirande, DO | TriHealth Inc. | Study Chair |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28792876 | Background | 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. | |
| 29634344 |
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| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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Not provided
| ID | Term |
|---|---|
| D009537 | Nicotinamide Mononucleotide |
| ID | Term |
|---|---|
| D012265 | Ribonucleotides |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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proof of concept
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|
| HLA-DR expression |
HLA-DR expression [healthy individuals <5-10% HLA DR CD 4+ T cell expression and <5%](streamdown:incomplete-link) |
| collected at baseline visit followed by monthly collections for total of 3 months |
| TNF-alpha | (Ref Interval: <=7.2) Cytokines- Results are used to understand the pathophysiology of immune, infectious, or inflammatory disorders | collected at baseline visit followed by monthly collections for total of 3 months |
| NAD(+) levels | Ranges from 10-500 µM during normal physiological state; however, it's levels can vary by age as well as metabolic and disease states | collected at baseline visit followed by monthly collections for total of 3 months |
| IL-6 | (Ref Interval: <=2.0 pg/mL ) Cytokines- Results are used to understand the pathophysiology of immune, infectious, or inflammatory disorders | collected at baseline visit followed by monthly collections for total of 3 months |
| HS-CRP | Ref Interval: <=3.0 mg/L | collected at baseline visit followed by monthly collections for total of 3 months |
| Changes on Quality-of-life Questionnaire (QOL): WHO QOL HIV BREF | Domain scores between 4-20 with higher score correlating with improved QOL | collected at baseline visit followed by monthly collections for total of 3 months |
| Background |
| 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. |
| 37619764 | Background | 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. |
| 25293882 | Background | 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. |
| 37980794 | Background | 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. |
| Background | 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). |
| 35222352 | Background | 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. |
| 37928477 | Background | 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. |
| 34306262 | Background | 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. |
| 31691351 | Background | 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. |
| 38155248 | Background | 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. |
| 35920870 | Background | 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. |
| D015229 |
| Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |