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

NCT06889142 | Not Yet Recruiting

• 1 other identifier: 24-089
• Study Type: interventional
• Target: 7
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Human Immunodeficiency Virus

Keywords

HIV; immunologic failure; proof of concept; CD4+ T cell recovery; immunological non-responders; Nicotinamide Mononucleotide

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• CD38

  collected at baseline visit followed by monthly collections for total of 3 months

• HLA-DR expression

  collected at baseline visit followed by monthly collections for total of 3 months

• TNF-alpha

  collected at baseline visit followed by monthly collections for total of 3 months

• NAD(+) levels

  collected at baseline visit followed by monthly collections for total of 3 months

• IL-6

  collected at baseline visit followed by monthly collections for total of 3 months

Study Arms (1)

Treatment with 1,000mg Nicotinamide Mononucleotide daily

EXPERIMENTAL

Dietary Supplement: Nicotinamide Mononucleotide

Interventions

Nicotinamide Mononucleotide DIETARY_SUPPLEMENT

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

Also known as: NMN

Treatment with 1,000mg Nicotinamide Mononucleotide daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• TriHealth Inc.: lead
• DoNotAge.org: collaborator

Related Publications (12)

• 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.

  PMID: 28792876 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.

  PMID: 29634344 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.

  PMID: 37619764 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.

  PMID: 25293882 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.

  PMID: 37980794 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).

  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.

  PMID: 35222352 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.

  PMID: 37928477 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.

  PMID: 34306262 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.

  PMID: 31691351 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.

  PMID: 38155248 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.

  PMID: 35920870 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Nicotinamide Mononucleotide

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleotides; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Madelyn Mirande, DO

  TriHealth Inc.

  STUDY CHAIR

Central Study Contacts

Martin L. Gnoni, MD

CONTACT

513-568-7462; martin_gnoni@trihealth.com

Madelyn Mirande, DO

CONTACT

715-307-1273; madelyn_mirande@trihealth.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: proof of concept

Study Record Dates

• First Submitted: March 3, 2025
• First Posted: March 21, 2025
• Study Start: April 1, 2025
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: April 3, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share