Clinical trial NCT05789355: Effect of NUV001 Supplementation in Patients Suffering From Sickle Cell Disease (SCD)
Official title: Effect of NUV001 Supplementation for 120 Days in Patients Suffering From Sickle Cell Disease (SCD) S Homozygous (SS) Genotype: A Pilot Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Sickle Cell Disease
Keywords: safety
tolerance
SS genotype of sickle cell disease
Lead sponsor: LGD
Sponsor class: INDUSTRY
Collaborators: name: CEN Biotech
name: Assistance Publique Hopitaux De Marseille
name: Etablissement Français du Sang
First posted: 2023-03-29
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-center, prospective, open-label pilot study.
Primary purpose: TREATMENT

Brief summary: This is a pilot study of daily dosing of NUV001 as a dietary supplement in 12 sickle cell disease patients with 3 months of follow-up plus 1 month after supplementation.The present study is designed to evaluate, first, the safety and tolerability parameters as well as to measure the plasma and urinary residues of daily oral doses of NUV001. Secondly, the study will evaluate the impact of NUV001 on biological parameters and quality of life of patients.

Detailed description: This is a monocentric, prospective, open label pilot study designed for 12 adult patients suffering of Sickle Cell disease (SCD) SS genotype each 12 receiving the active supplementation of NUV001, 1000mg/day (4 x 250 mg tablet) for 3 months of follow-up plus 1 month after supplementation. A stratification according to the medical treatment is planned. At least 2 patients suffering of SCD SS genotype without hydroxyurea treatment and maximum 10 patients suffering of SCD SS genotype in association with hydroxyurea treatment. If a subject is withdrawn from this study part, the subject may be replaced as necessary with another subject assigned to the same treatment at the discretion of the sponsor's team in consultation with the investigator.

The current study is designed to assess in the first part, the safety, tolerability, plasma, and urine residual rate parameters of daily oral doses of NUV001 as dietary supplement n adult patients suffering of sickle cell disease SS genotype. In a second part, the study will assess the pharmacological impact of NUV001 on biological parameters and the quality of life in patient suffering of sickle cell disease SS genotype.

Eligibility criteria: Inclusion Criteria:

1. Man or woman comprised between 18 and 60 years old.
2. Patients diagnosed with homozygous sickle cell anemia of SS genotype (documented by genotyping).
3. Females of childbearing potential should be using one of the following acceptable methods of birth control:

   * Intrauterine Device (IUD) in place for at least 60 days prior to the first dose of the study throughout the study and for 30 days after completion of the study.
   * Hormonal contraceptives for at least 90 days prior to the first dose of the study throughout the study, and for 30 days after study completion.
4. Patients whose weight is greater than 50 kg.
5. Patient that has been treated with an anti-sickling agent (Hydroxyurea) within six months of the screening visit, must maintain the therapy continuous and unmodified for at least six months with the intent to continue for the duration of the study.
6. Patient available to attend on an outpatient basis for visits provided for in the protocol and able to complete the data collection documents (and quality of life scale).
7. Patient has given written informed consent.
8. Patient with health insurance scheme

Exclusion Criteria:

1. Patient with known or suspected allergy to any ingredient of the food supplement .
2. Patient having consumed food supplements containing tryptophan, glutamine or vitamin B3 in its various forms (nicotinic acid/niacin and nicotinamide) during the month before selection
3. Patient has a significant medical condition that required hospitalization (other than sickle cell crisis) within two months of the screening visit.
4. Patient has serum albumin \< 3.0 g/dl.
5. Patient has been transfused and received any blood products within three months of the Screening Visit.
6. Patient has been hospitalized for acute vaso-occlusive crisis within one months of the Screening Visit.
7. Patient has clinically significant, cardiovascular or liver disease, renal or lung insufficiency or lymphopenia (with clinically significant abnormal results on the screening bioassays: complete blood count, transaminases (ASAT, ALAT, GGT, ALP), bilirubin, creatinine, CPK, Ionogram, blood glucose, lipid profile).
8. Patients with diagnosed cancer in the past 2 years
9. Pregnant or lactating woman. Woman of childbearing potential should have a negative (serum or urinary TBD) pregnancy test at screening and a negative urine pregnancy test at inclusion prior to administration of the Study Product.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: between Day 0 and Day 30
measure: Incidence of treatment-emergent adverse events
timeFrame: between Day 0 and Day 60
measure: Incidence of treatment-emergent adverse events
timeFrame: between Day 0 and Day 90
measure: Incidence of treatment-emergent adverse events
timeFrame: between Day 0 and Day 120
measure: Incidence of treatment-emergent clinically significant changes in clinical laboratory safety tests
timeFrame: between Day 0 and Day 30
measure: Incidence of treatment-emergent clinically significant changes in clinical laboratory safety tests
timeFrame: between Day 0 and Day 60
measure: Incidence of treatment-emergent clinically significant changes in clinical laboratory safety tests
timeFrame: between Day 0 and Day 90
measure: Incidence of treatment-emergent clinically significant changes in clinical laboratory safety tests
timeFrame: between Day 0 and Day 120
measure: Incidence of treatment-emergent clinically significant changes in Vital Signs
timeFrame: between Day 0 and Day 30
measure: Incidence of treatment-emergent clinically significant changes in Vital Signs
timeFrame: between Day 0 and Day 60
measure: Incidence of treatment-emergent clinically significant changes in Vital Signs
timeFrame: between Day 0 and Day 90
measure: Incidence of treatment-emergent clinically significant changes in Vital Signs
timeFrame: between Day 0 and Day 120
Secondary outcomes:
measure: Change in Lactate dehydrogenase (LDH) levels
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Change in Hemoglobin (HGB) levels
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Change in Hematocrit (HCT)
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Change in circulating level of red line cell precursors
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Change in mean corpuscular volume (MCV)
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Change in mean corpuscular hemoglobin content (MCHT)
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Change in reticulocyte level
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: F-Hemoglobin
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Circulating irreversibly sickle cells (ISCs)
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Red blood cells (RBC) sickling
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Nicotinamide adenine dinucleotide (NAD)+ concentration in whole blood
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: β-Nicotinamide mononucleotide (NMN) concentration in whole blood
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Methyl-Nicotinamide (Me-NAM) concentration in plasma
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Nicotinamide (NAM) concentration in plasma
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Nicotinamide (NAM) concentration in urine
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: N-Methyl-2-pyridone-5-carboxamide (2PY) concentration in urine
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
measure: Change from baseline of self-questionnaire quality of life 36-Item Short Form Survey (SF-36) version 1
timeFrame: Day 0, Day 15, Day 30, Day 60, Day 90, Day 120.
Other outcomes:
Locations:
city: Marseille
country: France
facility: Aphm Hopital La Timone Adultes Sce Medecine Interne (Umap)
Study officials:
affiliation: LGD SARL
name: Laurent LAGANIER
role: STUDY_DIRECTOR
affiliation: Assistance Publique Hopitaux Marseille
name: Estelle JEAN-MIGNARD
role: PRINCIPAL_INVESTIGATOR
References: