NCT06776510

A Clinical Study of NAD in the Treatment of Immune Thrombocytopenia

A Prospective, One-arm and Open Clinical Study to Assess Safety and Efficacy of Nicotinamide Adenine Dinucleotide in the Treatment of Primary Immune Thrombocytopenia

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To evaluate the safety and efficacy of nicotinamide adenine dinucleotide in the treatment of immune thrombocytopenia in patients who have not responded adequately or relapsed after first-line treatment and at least one second-line therapy including Anti-CD20 Antibody and/or TPO-RA.

Detailed description

Immune thrombocytopenia (ITP) is an organ-specific autoimmune disease, which is characterized by decreased platelet count and skin and mucosal bleeding. ITP is a kind of disease with increased platelet destruction and impaired platelet production caused by autoimmunity. Conventional treatment of adult ITP includes first-line glucocorticoid and immunoglobulin therapy, second line TPO and TPO receptor agonist, splenectomy and other immunosuppressive treatments (such as rituximab, vincristine, azathioprine, etc.). ITP is one of the most common hemorrhagic diseases. At present, the treatment response of ITP is not good, and a considerable number of patients need drug maintenance treatment, which seriously affects the quality of life of patients and increases the economic burden of patients. Therefore, there is still a lack of effective treatment for adult ITP, especially for recurrent and refractory ITP patients, which is one of the problems that have attracted more attention and need to be solved urgently. The main pathogenesis of ITP is the loss of platelet autoantigen immune tolerance, which leads to abnormal activation of humoral and cellular immunity. It is characterized by antibody mediated platelet destruction and insufficient platelet production by megakaryocytes. The residual long-term autoreactive plasma cells may be a source of therapeutic resistance to autoimmune cytopenia. Antiplatelet specific plasma cells have been detected in the spleen of patients with rituximab refractory ITP. Therefore, the strategy of simply eliminating B cells may not work, because LLPC will continue to produce pathogenic antibodies. However, targeting LLPC becomes a new strategy to treat autoimmune diseases. CM313, a kind of anti-CD38 antibody, is a new type of monoclonal antibody targeting CD38. It targets plasma cells and has carried out some clinical studies in multiple myeloma, with good therapeutic effects. We treated patients with refractory/relapsed ITP using CM313 and achieved good therapeutic outcomes, which may provide a new strategy for treating ITP. Current research shows that CD38, as a metabolic enzyme, can hydrolyze nicotinamide adenine dinucleotide (NAD+), leading to a decrease in intracellular NAD+. Additionally, during aging and inflammation, CD38 is highly expressed on macrophages, and the downregulation of NAD+ levels. Based on the current mechanistic studies of CD38 monoclonal antibody treatment for ITP, we found that macrophages in ITP patients exhibit a shift towards M1 polarization. We hypothesize that CD38 antibodies may reduce platelet destruction by macrophages by upregulating NAD+ levels, which in turn inhibits M1 polarization. Therefore, increasing NAD+ levels may have therapeutic potential for ITP. Since nicotinamide adenine dinucleotide (NAD+) has been used in clinical practice as an adjunctive treatment for leukopenia, coronary artery disease as well as myocarditis, and nicotinamide mononucleotide (NMN) has been explored in clinical trials, we will further investigate the therapeutic efficacy and safety of these compounds in ITP patients. Therefore, the investigators designed this clinical trial to evaluate the safety and efficacy of Nicotinamide Adenine Dinucleotide (Coenzyme I for Injection, NAD+) and nicotinamide mononucleotide (NMN) in the treatment of primary immune thrombocytopenia in patients who are steroid-refractory or steroid-dependent, and fail to respond to at least one previous second-line therapy, including rituximab and/ or TPO agonist.

Conditions

• Immune Thrombocytopenia
• Treatment

Interventions

Type	Name	Description
DRUG	nicotinamide adenine dinucleotid/nicotinamide mononucleotide	Drug: intravenous nicotinamide adenine dinucleotide (Coenzyme I for Injection) administration This study adopts a prospective, single arm, open design method. Twenty subjects were enrolled in the study and were treated with nicotinamide adenine dinucleotide (100mg/d) for 1 week. Drug: oral nicotinamide mononucleotide administration This study adopts a prospective, single arm, open design method. Twenty subjects were enrolled in the study and were treated with nicotinamide mononucleotide 450mg BID for 2 weeks. The first stage is the main research stage (d0-w2), which is the core treatment period. The aim is to observe the safety and efficacy during treatment. The second stage (w2-w8) is the stage of withdrawal from the visit, mainly to observe the safety and continuous efficacy after treatment.

Timeline

• Start date: 2025-01-15
• Primary completion: 2025-12-01
• Completion: 2026-03-01
• First posted: 2025-01-15
• Last updated: 2025-08-05

Locations

1 site across 1 country: China