Clinical trial NCT06445569: Safety and Efficacy of KH-1 for Stimulating Autophagy in Non-diabetic Adults With Elevated Blood Glucose Concentration
Official title: A Randomized, Double-blind, Placebo-controlled, Proof-of-concept Study to Evaluate the Safety and Efficacy of the Test Product KH-1 for Stimulating Autophagy in Non-diabetic Adults With Elevated Blood Glucose Concentration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: PreDiabetes
Aging
Keywords: Elevated Blood Glucose
Spermidine
Autophagy
Probiotic
Lead sponsor: Kalin Health, LLC
Sponsor class: INDUSTRY
Collaborators: name: Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
First posted: 2024-06-06
Enrollment: 42
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will consume their assigned study product for 3 months, after which all participants will be assigned to consume the KH-1 for the remaining 3 months in an open-label fashion.
Primary purpose: BASIC_SCIENCE

Brief summary: Aging significantly impacts overall health and is a risk factor for developing diabetes. An estimated 50% of U.S. adults aged ≥65 years were reported to have prediabetes (defined as having a fasting glucose concentration of 100-125 mg/dl) in 2005-2008. The Centers for Disease Control and Prevention (CDC) has stated that in the United States, 88 million people (one in every 3 Americans) are currently classified as prediabetic, emphasizing the importance of preventative measures and early intervention to manage and reduce the risk of progression to diabetes. Additionally, an estimated 430 million individuals worldwide are expected to have prediabetes by 2030. Dietary supplementation of polyamines, spermidine in particular, have been touted to have beneficial health effects such as increasing life span and mitigating impacts of aging. Spermidine and spermine are polyamines that are being increasingly investigated for their ability to slow the aging process by inducing autophagy. Nevertheless, literature on these topics is scarce and results from trials have been inconclusive; therefore further research is needed. The novel nutraceutical KH-1, comprised of spermidine, spermidine derivatives and probiotics, is examined in this trial of healthy volunteers aged 18 years or over. This study evaluates KH-1 for its safety and its effect on glucose homeostasis. This study measures the effects of KH-1 on biomarkers for inflammation, cardiovascular disease, insulin sensitivity, and those important for autophagy. A qualitative assessment of the effect of KH-1 on well-being is also examined.

Detailed description: Prediabetes is the intermediate state and precursor that can lead to an eventual diagnosis of diabetes. The presence of an elevated hemoglobin A1c (HbA1c), as well as insulin resistance with concomitant β-cell dysfunction is a strong indicator of prediabetes. Dietary and lifestyle changes are the most effective methods to control and prevent prediabetes, but maintenance of these changes is often difficult. Pharmaceutical options are indicated for treatment of diabetes rather than prevention of prediabetes, however many are associated with side effects. Therefore, a safe and effective alternative to prevent disease in metabolically dysregulated individuals is necessary.

The novel nutraceutical KH-1 is comprised of spermidine, amino acids, and a probiotic. This nutraceutical may offer a promising strategy for managing prediabetes.

This study is a double-blinded randomized controlled trial with 48 healthy volunteers to test the efficacy and safety of the novel nutraceutical KH-1. A total of 48 participants will be randomized in a double-blinded fashion, with 24 participants in each study group (KH-1 vs. placebo). After screening and randomization, participants will consume their assigned study product for 3 months, after which all participants will be assigned to consume the KH-1 for the remaining 3 months in an open-label fashion. Upon arrival at the clinic at the screening visit, participants will review the informed consent form (ICF), and if they agree to participate in the study, will sign and date the ICF, complete a brief screening, provide demographic information, and take part in other study activities indicated to be done on the screening visit. Participants who complete the screening process and qualify to continue are randomized to receive either the KH-1 or placebo in a 1:1 ratio for the first 3 months and assigned a unique randomization code. After the first 3 months, all participants will take KH-1. Participants will be instructed on the use of the nutraceutical product/placebo, according to label instructions. Participants will self-administer the study product at home and compliance will be assessed and documented at each visit. Venous blood samples will be collected at Week 0, Week 12 and Week 24 and analysed for biomarkers of glucose regulation and metabolism, cardiovascular health, inflammatory and autophagy biomarkers. Haematology and biochemistry parameters will be measured at screening, week 0, week 12 and week 24. A qualitative health questionnaire will be completed at 3 in-clinic visits and physical measurements to assess safety of the nutraceutical.

Eligibility criteria: Inclusion Criteria:

1. Healthy adult participants who are at least 50 years of age (inclusive) at the time of signing the informed consent form.
2. Have a body mass index (BMI) between 25.0 to 45.0 kg/m2 (inclusive).
3. In good general health and good oral health (no active or uncontrolled diseases, infections or conditions).
4. Impaired glucose metabolism evidence by either fasting glucose of 100 to 125 mg/dL at screening or an HbA1c between 5.7 and 6.4%.
5. Female participants of childbearing potential (i.e., participants who are not surgically sterilized or not post-menopausal (defined as amenorrhea for greater than 1 year), or transgendered males with retained ovaries and uterus) must agree to use a medically approved method of birth control for at least one month prior (or three months prior in the case of oral or long-acting injective contraceptives) to the first dose of study product and throughout the study, or abstain from heterosexual intercourse throughout the duration of the study and have a negative urine pregnancy result at baseline. For males of reproductive potential: use of condoms, abstinence from heterosexual intercourse, or other methods to ensure that their partners (if able) do not become pregnant during the course of the study.
6. Willing and able to agree to the requirements and restrictions of this study, be willing to give voluntary consent, be able to understand and read the questionnaires, and carry out all study-related procedures.

Exclusion criteria:

1. Participant has a medical history of uncontrolled hypertension (i.e., ≥160 mmHg systolic and/or ≥100 mmHg diastolic)
2. Participant has a medical history of heart disease and/or cardiovascular disease, kidney disease (dialysis or renal failure), hepatic impairment or disease, or Type 1 or Type 2 diabetes.
3. Participant has a medical history of unstable thyroid disease, previously diagnosed major affective disorder, psychiatric disorder that required hospitalization in the year prior to screening, immune disorder (i.e., HIV/AIDS), or a history of cancer (except localized skin cancer without metastases or in situ cervical cancer) within 5 years prior to screening visit.
4. Female participants who are lactating, pregnant, or planning to become pregnant during the study.
5. Have a known intolerance, sensitivity, or allergy to any of the study products or their ingredients, or any of the excipients used in the formulation.
6. Have a known intolerance, sensitivity, or allergy to milk.
7. Unable to be prescribed at least one of the antibiotics outlined in the study protocol.
8. Any condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the participant or the quality of the study data.
9. Currently taking dietary supplements other than vitamins (a 14-day washout period prior to baseline/Visit 2 would be permitted).
10. Taking any prescription medication at the time of randomization that is known to impact blood sugar and or blood sugar metabolism, as per Principal Investigator's (PI) discretion.
11. Use of certain medications in timeframes defined in the study protocol (Ampicillin, Gentamicin, Kanamycin, Streptomycin, Erythromycin, Clindamycin, Tetracycline, Chloramphenicol, Potassium sparing diuretics, Nitroglycerin and other nitrates, antidiabetic/Blood sugar lowering medications, any blood thinning medications (i.e., anticoagulant/antiplatelet drugs), antidepressants (use is permitted if dosage is maintained throughout the study), anxiolytics, antipsychotics , anticholinergics/antispasmodics, calcium-channel blockers (use is permitted if dosage is maintained throughout the study), Opioids.
12. Use of supplements dietary supplements/food/drink within 2 weeks or 7 half-lives (whichever is longer) prior to baseline and for the duration of the study, including foods/drinks rich in probiotics or prebiotics (e.g., yogurt, sauerkraut, kombucha) or synbiotics, Any herbs and supplements with hypoglycemic potential, any herbs or supplements that induce weight loss, any blood sugar lowering herbs or supplements, any blood thinning herbs or supplements
13. History of alcohol or substance abuse in the 12 months prior to screening.
14. Receipt or use of an investigational product in another research study within 28 days prior to baseline/Visit 2.

Primary outcomes:
measure: Insulin resistance
timeFrame: 3 months
measure: Insulin resistance
timeFrame: 3 months
measure: Insulin Resistance
timeFrame: 3 months
Secondary outcomes:
measure: Long-term effect on Insulin Resistance
timeFrame: 3 months
measure: Long-term effect on Insulin Resistance
timeFrame: 6 months
measure: Long-term effect on Insulin Resistance
timeFrame: 3 months
measure: Long-term effect on Insulin Resistance
timeFrame: 6 months
measure: Long-term effect on Insulin resistance
timeFrame: 3 months
measure: Long-term effect on Insulin Resistance
timeFrame: 6 months
measure: Post-prandial Glycemic Response
timeFrame: 3 months
measure: Post-prandial Glycemic Response
timeFrame: 3 months
measure: Post-prandial Glycemic Response
timeFrame: 6 months
measure: Post-prandial Glycemic Response
timeFrame: 3 months
measure: Post-prandial Glycemic Response
timeFrame: 3 months
measure: Post-prandial Glycemic Response
timeFrame: 6 months
measure: Glycemic Control
timeFrame: 3 months
measure: Glycemic Control
timeFrame: 3 months
measure: Glycemic Control
timeFrame: 6 months
measure: Glycemic Control
timeFrame: 3 months
measure: Glycemic Control
timeFrame: 3 months
measure: Glycemic Control
timeFrame: 6 months
measure: β-cell Function
timeFrame: 3 months
measure: β-cell Function
timeFrame: 3 months
measure: β-cell Function
timeFrame: 6 months
measure: Cardiovascular Biomarkers
timeFrame: 3 months
measure: Cardiovascular Biomarkers
timeFrame: 3 months
measure: Cardiovascular Biomarkers
timeFrame: 6 months
measure: Cardiovascular Biomarkers
timeFrame: 3 months
measure: Cardiovascular Biomarkers
timeFrame: 3 months
measure: Cardiovascular Biomarkers
timeFrame: 6 months
measure: Cardiovascular Biomarkers
timeFrame: 3 months
measure: Cardiovascular Biomarkers
timeFrame: 3 months
measure: Cardiovascular Biomarkers
timeFrame: 6 months
measure: Cardiovascular Biomarkers
timeFrame: 3 months
measure: Cardiovascular Biomarkers
timeFrame: 3 months
measure: Cardiovascular Biomarkers
timeFrame: 6 months
measure: Inflammatory Biomarkers
timeFrame: 3 months
measure: Inflammatory Biomarkers
timeFrame: 3 months
measure: Inflammatory Biomarkers
timeFrame: 6 months
measure: Inflammatory Biomarkers
timeFrame: 3 months
measure: Inflammatory Biomarkers
timeFrame: 3 months
measure: Inflammatory Biomarkers
timeFrame: 6 months
measure: Inflammatory Biomarkers
timeFrame: 3 months
measure: Inflammatory Biomarkers
timeFrame: 3 months
measure: Inflammatory Biomarkers
timeFrame: 6 months
measure: Autophagy
timeFrame: 3 months
measure: Autophagy
timeFrame: 3 months
measure: Autophagy
timeFrame: 6 months
measure: Immunity Biomarkers
timeFrame: 3 months
measure: Immunity Biomarkers
timeFrame: 3 months
measure: Immunity Biomarkers
timeFrame: 6 months
measure: Immunity Biomarkers
timeFrame: 3 months
measure: Immunity Biomarkers
timeFrame: 3 months
measure: Immunity Biomarkers
timeFrame: 6 months
measure: Immunity Biomarkers
timeFrame: 3 months
measure: Immunity Biomarkers
timeFrame: 3 months
measure: Immunity Biomarkers
timeFrame: 6 months
measure: Immunity Biomarkers
timeFrame: 3 months
measure: Immunity Biomarkers
timeFrame: 3 months
measure: Immunity Biomarkers
timeFrame: 6 months
measure: Overall Patient Health
timeFrame: 3 months
measure: Overall Patient Health
timeFrame: 3 months
measure: Overall Patient Health
timeFrame: 6 months
measure: Overall Quality of Life
timeFrame: 3 months
measure: Overall Quality of Life
timeFrame: 3 months
measure: Overall Quality of Life
timeFrame: 6 months
measure: Stress
timeFrame: 3 months
measure: Stress
timeFrame: 3 months
measure: Stress
timeFrame: 6 months
measure: Systolic Blood Pressure (SBP)
timeFrame: 6 months
measure: Diastolic Blood Pressure (DBP)
timeFrame: 6 months
measure: Heart Rate
timeFrame: 6 months
measure: Weight
timeFrame: 6 months
measure: Percent Body Fat
timeFrame: 6 months
measure: Body Mass Index (BMI)
timeFrame: 6 months
measure: Whole Blood Hemoglobin
timeFrame: 6 months
measure: Whole Blood Hematocrit
timeFrame: 6 months
measure: Whole Blood Red Blood Cell Count
timeFrame: 6 months
measure: Whole Blood Red Blood Cell Distribution Width
timeFrame: 6 months
measure: Whole Blood Mean Corpuscular Volume
timeFrame: 6 months
measure: Whole Blood Mean Corpuscular Hemoglobin
timeFrame: 6 months
measure: Whole Blood Mean Corpuscular Hemoglobin Concentration
timeFrame: 6 months
measure: Whole Blood White Blood Cells
timeFrame: 6 months
measure: Whole Blood Neutrophils
timeFrame: 6 months
measure: Whole Blood Basophils
timeFrame: 6 months
measure: Whole Blood Eosinophils
timeFrame: 6 months
measure: Whole Blood Lymphocytes
timeFrame: 6 months
measure: Whole Blood Monocytes
timeFrame: 6 months
measure: Whole Blood Mean Platelet Volume
timeFrame: 6 months
measure: Whole Blood Platelet Count
timeFrame: 6 months
measure: Serum Creatinine
timeFrame: 6 months
measure: Serum Blood Urea Nitrogen
timeFrame: 6 months
measure: Serum Alkaline Phosphatase (ALP)
timeFrame: 6 months
measure: Serum Asparatate Transaminase (AST)
timeFrame: 6 months
measure: Serum Alanine Transaminase (ALT)
timeFrame: 6 months
measure: Serum Albumin
timeFrame: 6 months
measure: Serum Total Protein
timeFrame: 6 months
measure: Serum Chloride
timeFrame: 6 months
measure: Serum Sodium
timeFrame: 6 months
measure: Serum Potassium
timeFrame: 6 months
measure: Serum Calcium
timeFrame: 6 months
measure: Serum Urea
timeFrame: 6 months
measure: Incidence of Adverse Events
timeFrame: 6 months
Other outcomes:
Locations:
city: Memphis
country: United States
facility: LifeDOC Research, PLLC
state: Tennessee
Study officials:
affiliation: LifeDOC Research, PLLC
name: Pedro Velasquez, MD
role: PRINCIPAL_INVESTIGATOR
References: