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Klotho Plasmid Gene Therapy for Prevention in Humans

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Study AimThis clinical trial aims to evaluate the safety and impact of Klotho plasmid gene therapy in humans for prevention purposes. We will measure changes in various biomarkers such as serum alpha-Klotho, FGF23, parathyroid hormone, vitamin D, phosphorus, and cystatin C levels, as well as monitor any adverse events.
What is being tested

Injectable Plasmid Klotho Gene Therapy

Genetic
Who is being recruted

Healthy Adults

From 23 to 90 Years
+9 Eligibility Criteria

See all eligibility criteria

How is the trial designed

Prevention Study

Phase 1
Interventional
Study Start: October 2025

See protocol details

Summary

Principal SponsorMinicircle
Study ContactMac Davis
Last updated: October 15, 2025
Sourced from a government-validated database.Claim as a partner
Study start date: October 6, 2025Actual date on which the first participant was enrolled.

This study aims to explore the safety and effects of a new gene therapy involving the Klotho gene. The Klotho gene is thought to be beneficial for improving memory, kidney function, and overall health and longevity. This investigation is especially relevant for healthy individuals, as the therapy's potential to enhance general health and cognitive abilities could lead to better quality of life and longer lifespan. Understanding these effects may also help in developing treatments for age-related health issues. Participants in this study will undergo various health and cognitive assessments both before and after receiving the gene therapy. The therapy is administered through a small injection into the fat of the abdomen. To measure the results, researchers will conduct blood tests, health screenings, and cognitive evaluations at multiple points during the study. Although the study takes place outside of the U.S. for the treatment portion, the evaluations before and after the treatment will occur in the U.S. The assessments aim to determine any improvements in health and cognitive functions after receiving the therapy.

Official TitleEvaluating the Safety and Efficacy of Injectable Klotho Plasmid Gene Therapy in Humans: An Interventional, Non-Placebo-Controlled Pilot Phase Study 
Principal SponsorMinicircle
Study ContactMac Davis
Last updated: October 15, 2025
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
24 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Prevention Study
Prevention studies aim to stop a disease from developing. They often involve people at risk and test things like vaccines, lifestyle changes, or preventive medications.

How participants are assigned to different groups/arms
In this clinical study, all participants receive the same treatment. Since there is only one group, there is no need for randomization or assignment to different arms. This type of study is often used to test a new treatment without comparing it to another.

Other Ways to Assign Participants
Randomized allocation: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.
Non-randomized allocation: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment: Participants are split into separate groups, each receiving a different treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
From 23 to 90 YearsRange of ages for which participants are eligible to join.
Healthy volunteers allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Healthy Adults
Criteria
4 inclusion criteria required to participate
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
5 exclusion criteria prevent from participating
Women of childbearing potential who are unwilling or unable to use effective contraception for the duration of the study
History of cancer diagnosis
Preexisting medical issues that may be exacerbated by the treatment
Has received any gene therapy within the past 12 months

Show More Criteria

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
One single intervention group 

is designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
This arm includes cognitive and health battery at multiple intervals pre- and post-administration of Klotho
Study Objectives
Primary Objectives

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.

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.

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.

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.

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.

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.

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.

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.
Secondary Objectives

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Serum ALT activity will be measured enzymatically and expressed in international units per liter (IU/L). ALT serves as a marker of hepatocellular injury.

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.

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.

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.

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.

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.

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.

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.

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.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 2 locations
Recruiting
Apeiron CenterAustin, United StatesSee the location
Recruiting soon
GARM ClinicRoatán, Honduras
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2 Study Centers