Evaluating the Safety and Efficacy of Injectable Combination Klotho and Follistatin Plasmid Gene Therapy in Humans -- An Interventional, Non-Placebo Controlled Pilot Phase Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 4
- 主要终点
- Concentration of Serum α-Klotho Measured by Enzyme-Linked Immunosorbent Assay (ELISA) (pg/mL)
研究概览
简要总结
The purpose of this study is to investigate the safety and efficacy of a combination klotho and follistatin gene therapy, delivered via a nonviral plasmid in healthy adult volunteers. Additionally, this study seeks to understand the cognitive and health benefits of this gene therapy.
详细描述
Healthy participants will take part in cognitive and health testing before and after administration of plasmid-delivered nonviral klotho and follistatin gene therapy. The method of administration will be subcutaneous injection into abdominal fat deposits. Klotho and follistatin plasmid gene therapy have the potential to improve physical function, cognitive function, kidney function, body composition, epigenetic age, and subjective well being.
Note that the investigational product will be administered at a site outside of the U.S. which is not under FDA jurisdiction, and only non-treatment pre/post outcome assessments (e.g., cognitive assessments or blood sample collection) occur at the U.S. site.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults aged 50 to 80 years
- •General good health
- •Willing to comply with all study-related procedures and visits
- •Participant is open to morphological change
- •If female, participant agrees to maintain contraception
- •If female, participant agrees to take a pregnancy test
- •If female, participant agrees to a pregnancy waiver
排除标准
- •Currently enrolled in another clinical trial
- •History of cancer, autoimmune disease, or chronic kidney/liver disease
- •Use of immunosuppressive therapy
- •Pregnant or breastfeeding
- •Women of childbearing potential who are unwilling or unable to use effective contraception for the duration of the study.
- •Regular use of NMDA (N-methyl-D-aspartate) antagonists (i.e., memantine, ketamine, etc.)
- •Regular use of antiplatelet medications (i.e., aspirin)
- •Any medical or psychiatric condition that could interfere with participation or pose safety concerns
- •Unwilling or unable to provide informed consent
研究组 & 干预措施
Intervention with Cognitive/Health battery before and after
This arm includes cognitive and health battery pre- and post-intervention of the gene therapy
干预措施: Follistatin and klotho gene therapy (Genetic)
结局指标
主要结局
Concentration of Serum α-Klotho Measured by Enzyme-Linked Immunosorbent Assay (ELISA) (pg/mL)
时间窗: From 1 month prior to treatment to 3 months after treatment (5 timepoints)
Serum α-Klotho protein concentration will be quantified using a validated ELISA. Results will be determined from picograms per milliliter (pg/mL) for each participant at each time point. Higher or lower values have no inherent directionality and will be interpreted in study context.
Concentration of Serum Follistatin Measured by Enzyme-Linked Immunosorbent Assay (ELISA) (pg/mL)
时间窗: From 1 month prior to treatment to 3 months after treatment (5 timepoints)
Serum follistatin concentration will be quantified using a validated ELISA. Results will be reported as picograms per milliliter (pg/mL) for each participant at each time point. Higher or lower values have no inherent directionality and will be interpreted in study context.
Number and Percentage of Participants Experiencing Treatment-Emergent Adverse Events as Assessed by Patient-Reported Outcomes Version of Common Terminology Criteria for Adverse Events (PRO-CTCAE)
时间窗: Within 1 week after treatment and then 1 month, 2 months, and 3 months after treatment
Assessed through a checklist version of the PRO-CTCAE with each symptom options being none, mild, moderate, or severe. Items will be scored with 0, 1, 2, 3 respectively. Item responses will be summarized as number and percentage of participants experiencing each adverse event by system/organ class. High scores indicate highest severity of symptoms and low scores indicate no symptoms.
次要结局
- Change From Baseline in World Health Organization Quality of Life Brief Version (WHOQOL-BREF) Domain Scores (0-100)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Change from baseline in number of squats performed (count)(From 1 month prior to treatment to 3 months after treatment (4 timepoints))
- Concentration of Ionized Calcium Measured by Ion-Selective Electrode (mmol/L)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Change From Baseline in Pattern Comparison Processing Speed Test T-Score (Mean 50 ± 10)(From 1 month prior to treatment to 3 months after treatment (4 timepoints))
- Number of sit-ups performed (change from baseline) (count)(From 1 month prior to treatment to 3 months after treatment (4 timepoints))
- Change From Baseline in Dimensional Change Card Sort Test T-Score (Mean 50 ± 10)(From 1 month prior to treatment to 3 months after treatment (4 timepoints))
- Change From Baseline in Picture Sequence Memory Test T-Score, Forms A and B (Mean 50 ± 10)(From 1 month prior to treatment to 3 months after treatment (4 timepoints))
- Epigenetic Biological Age Estimated From Whole-Genome Deoxyribonucleic Acid (DNA) Methylation Profiles (change from baseline) (years)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Change from baseline in number of push-ups performed (count)(From 1 month prior to treatment to 3 months after treatment (4 timepoints))
- Change from Baseline: Concentration of High-Sensitivity C-Reactive Protein (hs-CRP) Measured by Immunoturbidimetric Assay (mg/L)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Change From Baseline in Flanker Inhibitory Control and Attention Test T-Score (Mean 50 ± 10)(From 1 month prior to treatment to 3 months after treatment (4 timepoints))
- Change From Baseline in Picture Vocabulary Test T-Score (Mean 50 ± 10)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Timed one leg stance change from baseline (seconds)(From 1 month prior to treatment to 3 months after treatment (4 timepoints))
- Comprehensive Metabolic Panel (Safety Laboratory Assessment)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Hemoglobin A1c (%) change from baseline(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Myostatin (ng/mL)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Concentration of Serum Cystatin C Measured by Immunoassay (mg/L)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Concentration of Serum Phosphorus Measured by Clinical Chemistry Analyzer (mg/dL)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Urinary Phosphate Excretion Measured by Clinical Chemistry Assay (mg/24 h or mg/g Creatinine)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Serum Interleukin-1β (IL-1β) change from baseline (pg/mL)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Concentration of Intact Parathyroid Hormone Measured by Two-Site Immunoassay (pg/mL)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Concentration of Serum 1,25-Dihydroxyvitamin D (Calcitriol) Measured by Liquid Chromatography-Tandem Mass Spectrometry (pg/mL)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Concentration of Platelet Factor 4 (PF4) Measured by Enzyme-Linked Immunosorbent Assay (ELISA) (ng/mL or OD Units)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Cardio IQ® Fibrinogen Antigen (mg/dL)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Homocysteine change from baseline (µmol/L)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Asymmetric and Symmetric Dimethylarginine (ADMA/SDMA) change from baseline (µmol/L)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Serum Interleukin-6 (IL-6) change from baseline (pg/mL)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Tumor Necrosis Factor-α (TNF-α) change from baseline (pg/mL)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Serum Interferon-γ (IFN-γ) (pg/mL)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Activin A (pg/mL)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Insulin-Like Growth Factor-1 (IGF-1) (ng/mL)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))
- Serum Interleukin-10 (IL-10) (pg/mL)(From 1 month prior to treatment to 3 months after treatment (5 timepoints))