A Phase 1 interventional study of Injectable Plasmid Klotho Gene Therapy in Healthy Adults, sponsored by Minicircle. Active, not recruiting at 2 sites in 2 countries. Open to participants aged 23 Years to 90 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-27.
Sponsored by Minicircle · Phase 1, Interventional, and Prevention
The purpose of this study is to investigate the safety and efficacy of a gene therapy for Klotho, delivered via a nonviral plasmid in healthy adult volunteers. Additionally, this study seeks to understand the cognitive and health benefits of the Klotho gene therapy.
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.
Participants will take part in cognitive and health testing before and after administration of plasmid-delivered Klotho gene therapy. The method of administration will be subcutaneous injection into abdominal fat deposits. Klotho may improve cognitive function, kidney function, healthspan, and lifespan. Healthy volunteers will partake in a series of blood draws, health screenings, questionnaires, brain perfusion/function measures, and cognitive testing multiple times before and after the intervention.
Minicircle is the lead sponsor of 3 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
This arm includes cognitive and health battery at multiple intervals pre- and post-administration of Klotho
Genetic: Injectable Plasmid Klotho Gene Therapy
Injection of plasmid-delivered Klotho gene therapy
Concentration of Serum α-Klotho Measured by Enzyme-Linked Immunosorbent Assay (pg/mL)
Serum α-Klotho protein concentration will be quantified using a validated enzyme-linked immunosorbent assay (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.
Time frame: Measured 1 month before and 7 days before injection, then 3 days, 7 days, 1 month, 3 months, 6 months after
Adverse Events: Number and Percentage of Participants Experiencing Treatment-Emergent Adverse Events as Assessed Patient-Reported Outcomes Version of Common Terminology Criteria for Adverse Events (PRO-CTCAE)
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.
Time frame: Measured 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Serum Fibroblast Growth Factor 23 (FGF23) Measured by Enzyme-Linked Immunosorbent Assay (pg/mL)
Fibroblast Growth Factor 23 (FGF23) concentration will be quantified in serum using a validated enzyme-linked immunosorbent assay (ELISA). Results will be expressed in picograms per milliliter (pg/mL) for each participant and time point. FGF23 is a downstream effector of α-Klotho signaling and reflects activity of the phosphate-vitamin D regulatory axis.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Intact Parathyroid Hormone Measured by Two-Site Immunoassay (pg/mL)
Intact Parathyroid Hormone (PTH) will be measured in serum using a two-site immunoassay that detects the full-length molecule. Results will be reported in picograms per milliliter (pg/mL) per participant and time point. PTH reflects parathyroid activity within the α-Klotho-FGF23-vitamin D feedback pathway.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Serum 1,25-Dihydroxyvitamin D (Calcitriol) Measured by Liquid Chromatography-Tandem Mass Spectrometry (pg/mL)
Serum 1,25-dihydroxyvitamin D (calcitriol) will be quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Concentrations will be expressed in picograms per milliliter (pg/mL). This hormone regulates calcium and phosphate balance and is a downstream marker of α-Klotho-FGF23-PTH axis modulation.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Serum Phosphorus Measured by Clinical Chemistry Analyzer (mg/dL)
Serum inorganic phosphorus will be measured on a standard clinical chemistry analyzer. Results will be reported in milligrams per deciliter (mg/dL) for each participant and time point. Phosphorus levels reflect systemic phosphate homeostasis influenced by α-Klotho and FGF23 activity.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Urinary Phosphate Excretion Measured by Clinical Chemistry Assay (mg/24 h or mg/g Creatinine)
Urinary phosphate will be assessed using a validated chemistry assay. Results will be expressed either as total phosphate excretion in milligrams per 24 hours (mg/24 h) or as the phosphate-to-creatinine ratio (mg phosphate per g creatinine). This measure reflects renal handling of phosphate and functional effects of α-Klotho on phosphate excretion.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Serum Cystatin C Measured by Immunoassay (mg/L)
Serum Cystatin C will be measured using a standardized immunoassay and reported in milligrams per liter (mg/L) for each participant and time point. Cystatin C serves as a biomarker of glomerular filtration rate and provides a mechanistic link between α-Klotho activity and renal function.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Change From Baseline in World Health Organization Quality of Life Brief Version Domain Scores (0-100)
The World Health Organization Quality of Life Brief Version (WHOQOL-BREF) is a self-report questionnaire that includes four domains: Physical Health, Psychological, Social Relationships, and Environment. Each domain score is transformed to a 0-100 scale, with higher scores indicating better quality of life. Changes from baseline will be reported for each domain separately.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 month, 6 months after.
Change From Baseline in Flanker Inhibitory Control and Attention Test T-Score (Mean 50 ± 10)
The Flanker Inhibitory Control and Attention Test measures inhibitory control and attention. Scores are age-adjusted T-scores (mean 50, SD 10). Higher scores indicate better performance. Changes from baseline will be analyzed per participant and time point.
Time frame: Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment.
Change From Baseline in Dimensional Change Card Sort Test T-Score (Mean 50 ± 10)
The Dimensional Change Card Sort Test assesses cognitive flexibility. Scores are age-adjusted T-scores (mean 50, SD 10). Higher scores indicate better executive function. Changes from baseline will be analyzed per participant and time point.
Time frame: Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment.
Change From Baseline in Pattern Comparison Processing Speed Test T-Score (Mean 50 ± 10)
The Pattern Comparison Processing Speed Test measures processing speed using age-adjusted T-scores (mean 50, SD 10). Higher scores reflect faster cognitive processing. Changes from baseline will be analyzed per participant and time point.
Time frame: Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment.
Change From Baseline in Picture Sequence Memory Test T-Score, Forms A and B (Mean 50 ± 10)
Picture Sequence Memory Test evaluates episodic memory. Each form (A and B) yields an age-adjusted T-score (mean 50, SD 10). Higher scores indicate better memory performance. Forms A and B will be averaged.
Time frame: Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment.
Change From Baseline in Picture Vocabulary Test T-Score (Mean 50 ± 10)
Picture Vocabulary Test measures receptive vocabulary. Results are expressed as age-adjusted T-scores (mean 50, SD 10), with higher scores indicating better performance. Change from baseline will be analyzed per participant and time point.
Time frame: Measured 7 days before, then 3 days, 7 days, 1 month, 3 months, 6 months after treatment.
Change From Baseline in Reynolds Intellectual Assessment Scales-Second Edition (RIAS-2) Composite Scores (Standard Score Mean 100 ± 15)
The Reynolds Intellectual Assessment Scales-Second Edition (RIAS-2) measures verbal, nonverbal, and composite intelligence. Each index yields a standard score (mean 100, SD 15) and subtests yield scaled scores (mean 10, SD 3). Higher scores indicate better cognitive performance. Changes from baseline will be reported for each selected index separately.
Time frame: Measured 1 month before and then 1 month and 3 months after.
Concentration of Serum Glucose Measured by Clinical Chemistry Analyzer (mg/dL)
Serum glucose will be measured using a standard clinical chemistry analyzer and expressed in milligrams per deciliter (mg/dL). Elevated glucose may indicate altered carbohydrate metabolism or metabolic stress.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Total Serum Calcium Measured by Clinical Chemistry Analyzer (mg/dL)
Total calcium will be quantified using a colorimetric method on a clinical chemistry analyzer. Results will be expressed in milligrams per deciliter (mg/dL). Calcium levels reflect bone-mineral balance and parathyroid function.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Ionized Calcium Measured by Ion-Selective Electrode (mmol/L)
Ionized calcium will be measured using an ion-selective electrode analyzer. Results will be reported in millimoles per liter (mmol/L) and represent physiologically active calcium fraction.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Serum Sodium Measured by Ion-Selective Electrode (mmol/L)
Sodium concentration will be measured using an ion-selective electrode analyzer and expressed in millimoles per liter (mmol/L). Sodium reflects hydration and electrolyte balance.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Serum Potassium Measured by Ion-Selective Electrode (mmol/L)
Serum potassium will be quantified using an ion-selective electrode analyzer and expressed in millimoles per liter (mmol/L). Potassium levels reflect renal and electrolyte homeostasis.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Serum Chloride Measured by Ion-Selective Electrode (mmol/L)
Serum chloride will be measured using an ion-selective electrode analyzer. Results will be expressed in millimoles per liter (mmol/L) and reflect acid-base and hydration status.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Serum Bicarbonate (CO₂) Measured by Clinical Chemistry Analyzer (mmol/L)
Serum bicarbonate will be measured as total CO₂ on a clinical chemistry analyzer. Results will be expressed in millimoles per liter (mmol/L) and indicate systemic acid-base balance.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Blood Urea Nitrogen (BUN) Measured by Clinical Chemistry Analyzer (mg/dL)
Blood urea nitrogen (BUN) will be measured using a standard enzymatic assay and expressed in milligrams per deciliter (mg/dL). BUN reflects renal function and nitrogen metabolism.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Serum Creatinine Measured by Clinical Chemistry Analyzer (mg/dL)
Serum creatinine will be measured using a validated enzymatic method on a clinical chemistry analyzer. Results will be reported in milligrams per deciliter (mg/dL) and serve as an indicator of renal filtration.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Serum Albumin Measured by Clinical Chemistry Analyzer (g/dL)
Serum albumin will be quantified using a bromocresol green dye-binding method and expressed in grams per deciliter (g/dL). Albumin reflects nutritional status and hepatic synthetic function.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Total Serum Protein Measured by Biuret Method (g/dL)
Total protein will be measured using the biuret colorimetric assay and expressed in grams per deciliter (g/dL). This parameter provides an overview of plasma protein balance.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Alkaline Phosphatase (ALP) Measured by Clinical Chemistry Analyzer (IU/L)
Serum alkaline phosphatase will be quantified by an enzymatic colorimetric method and expressed in international units per liter (IU/L). ALP reflects hepatobiliary and bone function.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Alanine Aminotransferase (ALT) Measured by Clinical Chemistry Analyzer (IU/L)
Serum ALT activity will be measured enzymatically and expressed in international units per liter (IU/L). ALT serves as a marker of hepatocellular injury.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Aspartate Aminotransferase (AST) Measured by Clinical Chemistry Analyzer (IU/L)
Serum AST activity will be determined by an enzymatic method and expressed in international units per liter (IU/L). AST reflects hepatic and, to a lesser extent, cardiac or muscle integrity.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Total Serum Bilirubin Measured by Diazo Method (mg/dL)
Total bilirubin will be measured using a diazo-based colorimetric assay and expressed in milligrams per deciliter (mg/dL). Bilirubin serves as an indicator of liver function and hemolysis.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of High-Sensitivity C-Reactive Protein (hs-CRP) Measured by Immunoturbidimetric Assay (mg/L)
High-sensitivity C-reactive protein will be measured using an immunoturbidimetric assay and expressed in milligrams per liter (mg/L). hs-CRP serves as a marker of systemic inflammation and cardiovascular risk.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Asymmetric Dimethylarginine (ADMA) Measured by Liquid Chromatography-Tandem Mass Spectrometry (µmol/L)
Asymmetric dimethylarginine (ADMA) will be quantified using LC-MS/MS and expressed in micromoles per liter (µmol/L). ADMA reflects endothelial function and nitric oxide metabolism.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Concentration of Platelet Factor 4 (PF4) Measured by Enzyme-Linked Immunosorbent Assay (ng/mL or OD Units)
Platelet Factor 4 (PF4) will be measured using a validated ELISA. Results will be reported as nanograms per milliliter (ng/mL) or optical density (OD) units, depending on assay type. PF4 is a marker of platelet activation and potential immune-mediated coagulation effects.
Time frame: Measured 1 month before, 7 days before, and then 3 days, 7 days, 1 month, 3 months, and 6 months after treatment.
Epigenetic Biological Age Estimated From Whole-Genome DNA Methylation Profiles (years)
Whole-blood DNA methylation will be measured using bisulfite sequencing performed by Generation Lab. Epigenetic biological age will be computed from these methylation data using validated algorithms. Age estimates will be expressed in years. Lower epigenetic age relative to chronological age indicates younger biological status.
Time frame: Measured 7 days before administration and then 3 days, 7 days, 1 month, 3 months, and 6 months after administration
Estimated Brain Age: Derived From Kernel Flow Functional Near-Infrared Spectroscopy (fNIRS) Analysis (years)
Resting-state cerebral hemodynamic activity will be measured using the Kernel Flow headset, which integrates time-domain functional near-infrared spectroscopy (TD-fNIRS) and behavioral data. Kernel's proprietary machine learning algorithms will process whole-brain optical signals to generate an Estimated Brain Age, expressed in years. The metric represents the predicted biological brain age relative to chronological age, derived from composite models trained on resting-state fNIRS and behavioral features. Lower Estimated Brain Age values indicate more youthful brain function. Data will be reported per participant at baseline and after treatment.
Time frame: Measured 7 days before and then 3 days, 7 days, 1 month, and 3 months after treatment
Cognitive Performance Index and Domain Percentiles Derived From Kernel Flow functional near-infrared spectroscopy (fNIRS) and Behavioral Metrics (percentile where higher = better)
Cognitive performance will be assessed using Kernel Flow's composite metrics derived from time-domain functional near-infrared spectroscopy (TD-fNIRS) and brief behavioral tasks. Domain-specific percentile scores will be generated for Complex Attention, Executive Function, Learning and Memory, Language, and Perceptual-Motor Control, as well as an overall Cognitive Performance Index. Each score reflects age-normed percentile performance, integrating brain and behavioral features using Kernel's proprietary machine learning models. Higher percentiles indicate better cognitive performance relative to age-matched norms. Metrics will be reported per participant at baseline and after treatment.
Time frame: Measured 7 days before and then 3 days, 7 days, 1 month, and 3 months after treatment
Plan to share: Yes — Individual participant data will be made available along with a data dictionary describing each variable. If the study results in multiple publications, the IPD corresponding to the measures reported in each publication will be shared upon that publication. The complete trial dataset, if anything is remaining, will be made available once all results have been published. Supporting documentation shared will include study protocol, statistical analysis plan, informed consent forms, and analytic code.
Supporting information: Study protocol, Statistical analysis plan, Analytic code
Time frame: Data will be made available upon publication and will be available indefinitely.
Access criteria: Data will be made available to anyone who wishes to access it in an online repository at Vivli (https://vivli.org/). The types of data shared will include de-identified data of pre- and post-treatment values for the following measures: serum Klotho levels; kidney and blood safety panels; questionnaires and adverse event reporting data (all check box questions; however, any open-ended answer data will reviewed to ensure they cannot be used to identify an individual participant - final judgments will be made by the study central coordinator); RIAS-2 scores; all NIH-toolbox measures; Kernel brain data; epigenetic age.
Started Oct 2025 (actual). Primary completion is estimated for Aug 2026, 10 months after the start.
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