Safety and Efficacy of KH-1 for Stimulating Autophagy in Non-diabetic Adults With Elevated Blood Glucose Concentration

Aging Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06445569
• Other study ID #: K02-21-01-T0012
• Status: Completed
• Phase: N/A
• Start date: December 20, 2021
• Est. completion date: June 8, 2023

Study information

• Verified date: May 2024
• Source: Kalin Health, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: June 8, 2023
• Est. primary completion date: June 8, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Aging
• Hyperglycemia
• PreDiabetes

Intervention

Dietary Supplement:
• KH-1
3 capsules and one stick packet consumed daily around the same time

Other:
• Placebo
3 capsules and one stick packet consumed daily around the same time

Locations

Country	Name	City	State
United States	LifeDOC Research, PLLC	Memphis	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Kalin Health, LLC	Nutrasource Pharmaceutical and Nutraceutical Services, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin resistance	Between placebo and test product, change from baseline to 3 months in fasting insulin	3 months
Primary	Insulin resistance	Between placebo and test product, change from baseline to 3 months in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	3 months
Primary	Insulin Resistance	Between placebo and test product, change from baseline to 3 months Oral Glucose Tolerance Test (OGTT)- derived indices of insulin dynamics	3 months
Secondary	Long-term effect on Insulin Resistance	Within-group change from baseline to 3 months for fasting insulin	3 months
Secondary	Long-term effect on Insulin Resistance	Within-group change from baseline to 6 months for fasting insulin	6 months
Secondary	Long-term effect on Insulin Resistance	Within-group change from baseline to 3 months for HOMA-IR	3 months
Secondary	Long-term effect on Insulin Resistance	Within-group change from baseline to 6 months for HOMA-IR	6 months
Secondary	Long-term effect on Insulin resistance	Within-group change from baseline to 3 months for OGTT-derived indices	3 months
Secondary	Long-term effect on Insulin Resistance	Within-group change from baseline to 6 months for OGTT-derived indices	6 months
Secondary	Post-prandial Glycemic Response	Between placebo and test product, change from baseline to 3 months in area under the glucose concentration (AUC) post-OGTT	3 months
Secondary	Post-prandial Glycemic Response	Within-group change from baseline to 3 months in area under the glucose concentration (AUC) post-OGTT	3 months
Secondary	Post-prandial Glycemic Response	Within-group change from baseline to 6 months in area under the glucose concentration (AUC) post-OGTT	6 months
Secondary	Post-prandial Glycemic Response	Between placebo and test product, change from baseline to 3 months in 2-hour post-prandial glucose	3 months
Secondary	Post-prandial Glycemic Response	Within-group change from baseline to 3 months in 2-hour post-prandial glucose	3 months
Secondary	Post-prandial Glycemic Response	Within-group change from baseline to 6 months in 2-hour post-prandial glucose	6 months
Secondary	Glycemic Control	Between placebo and test product, change from baseline to 3 months in fasting glucose	3 months
Secondary	Glycemic Control	Within-group change from baseline to 3 months in fasting glucose	3 months
Secondary	Glycemic Control	Within-group change from baseline to 6 months in fasting glucose	6 months
Secondary	Glycemic Control	Between placebo and test product, change from baseline to 3 months in HbA1c	3 months
Secondary	Glycemic Control	Within-group change from baseline to 3 months in HbA1c	3 months
Secondary	Glycemic Control	Within-group change from baseline to 6 months in HbA1c	6 months
Secondary	ß-cell Function	Between placebo and test product, change from baseline to 3 months in oral disposition index (DI) calculated by the ratio of the insulinogenic index over fasting insulin	3 months
Secondary	ß-cell Function	Within-group change from baseline to 3 months in oral DI	3 months
Secondary	ß-cell Function	Within-group change from baseline to 6 months in oral DI	6 months
Secondary	Cardiovascular Biomarkers	Between placebo and test product, change from baseline to 3 months in fasting triglycerides (TG)	3 months
Secondary	Cardiovascular Biomarkers	Within-group change from baseline to 3 months in fasting TG	3 months
Secondary	Cardiovascular Biomarkers	Within-group change from baseline to 6 months in fasting TG	6 months
Secondary	Cardiovascular Biomarkers	Between placebo and test product, change from baseline to 3 months in fasting total cholesterol	3 months
Secondary	Cardiovascular Biomarkers	Within-group change from baseline to 3 months in fasting total cholesterol	3 months
Secondary	Cardiovascular Biomarkers	Within-group change from baseline to 6 months in fasting total cholesterol	6 months
Secondary	Cardiovascular Biomarkers	Between placebo and test product, change from baseline to 3 months in fasting low-density lipoprotein (LDL)	3 months
Secondary	Cardiovascular Biomarkers	Within-group change from baseline to 3 months in fasting LDL	3 months
Secondary	Cardiovascular Biomarkers	Within-group change from baseline to 6 months in fasting LDL	6 months
Secondary	Cardiovascular Biomarkers	Between placebo and test product, change from baseline to 3 months in high-density lipoprotein (HDL)	3 months
Secondary	Cardiovascular Biomarkers	Within-group change from baseline to 3 months in HDL	3 months
Secondary	Cardiovascular Biomarkers	Within-group change from baseline to 6 months in HDL	6 months
Secondary	Inflammatory Biomarkers	Between placebo and test product, change from baseline to 3 months in high-sensitivity C-reactive protein (hs-CRP)	3 months
Secondary	Inflammatory Biomarkers	Within-group change from baseline to 3 months in hs-CRP	3 months
Secondary	Inflammatory Biomarkers	Within-group change from baseline to 6 months in hs-CRP	6 months
Secondary	Inflammatory Biomarkers	Between placebo and test product, change from baseline to 3 months in tumor necrosis factor (TNF)-alpha	3 months
Secondary	Inflammatory Biomarkers	Within-group change from baseline to 3 months in TNF-alpha	3 months
Secondary	Inflammatory Biomarkers	Within-group change from baseline to 6 months in TNF-alpha	6 months
Secondary	Inflammatory Biomarkers	Between placebo and test product, change from baseline to 3 months in interleukin-6 (IL-6)	3 months
Secondary	Inflammatory Biomarkers	Within-group change from baseline to 3 months in IL-6	3 months
Secondary	Inflammatory Biomarkers	Within-group change from baseline to 6 months in IL-6	6 months
Secondary	Autophagy	Between placebo and test product, change from baseline to 3 months in Beclin-1	3 months
Secondary	Autophagy	Within-group change from baseline to 3 months in Beclin-1	3 months
Secondary	Autophagy	Within-group change from baseline to 6 months in Beclin-1	6 months
Secondary	Immunity Biomarkers	Between placebo and test product, change from baseline to 3 months in Cluster of Differentiation (CD) 3	3 months
Secondary	Immunity Biomarkers	Within-group change from baseline to 3 months in CD3	3 months
Secondary	Immunity Biomarkers	Within-group change from baseline to 6 months in CD3	6 months
Secondary	Immunity Biomarkers	Between placebo and test product, change from baseline to 3 months in CD4	3 months
Secondary	Immunity Biomarkers	Within-group change from baseline to 3 months in CD4	3 months
Secondary	Immunity Biomarkers	Within-group change from baseline to 6 months in CD4	6 months
Secondary	Immunity Biomarkers	Between placebo and test product, change from baseline to 3 months in CD8	3 months
Secondary	Immunity Biomarkers	Within-group change from baseline to 3 months in CD8	3 months
Secondary	Immunity Biomarkers	Within-group change from baseline to 6 months in CD8	6 months
Secondary	Immunity Biomarkers	Between placebo and test product, change from baseline to 3 months in CD25	3 months
Secondary	Immunity Biomarkers	Within-group change from baseline to 3 months in CD25	3 months
Secondary	Immunity Biomarkers	Within-group change from baseline to 6 months in CD25	6 months
Secondary	Overall Patient Health	Between placebo and test product, change from baseline to 3 months in Patient Health Questionnaire scores	3 months
Secondary	Overall Patient Health	Within-group change from baseline to 3 months in Patient Health Questionnaire scores	3 months
Secondary	Overall Patient Health	Within-group change from baseline to 6 months in Patient Health Questionnaire scores	6 months
Secondary	Overall Quality of Life	Between placebo and test product, change from baseline to 3 months in RAND-36 questionnaire scores	3 months
Secondary	Overall Quality of Life	Within-group change from baseline to 3 months in RAND-36 questionnaire scores	3 months
Secondary	Overall Quality of Life	Within-group change from baseline to 6 months in RAND-36 questionnaire scores	6 months
Secondary	Stress	Between placebo and test product, change from baseline to 3 months in Perceived Stress Scale (PSS) scores	3 months
Secondary	Stress	Within-group change from baseline to 3 months in PSS scores	3 months
Secondary	Stress	Within-group change from baseline to 6 months in PSS scores	6 months
Secondary	Systolic Blood Pressure (SBP)	Change from baseline to 6 months in SBP (mmHg)	6 months
Secondary	Diastolic Blood Pressure (DBP)	Change from baseline to 6 months in DBP (mmHg)	6 months
Secondary	Heart Rate	Change from baseline to 6 months in heart rate (beats per minute)	6 months
Secondary	Weight	Change from baseline to 6 months in weight (kg)	6 months
Secondary	Percent Body Fat	Change from baseline to 6 months in percent body fat (%)	6 months
Secondary	Body Mass Index (BMI)	Change from baseline to 6 months in BMI (kg/m2)	6 months
Secondary	Whole Blood Hemoglobin	Change from baseline in fasting whole blood hemoglobin (g/dL)	6 months
Secondary	Whole Blood Hematocrit	Change from baseline in fasting whole blood hematocrit (%)	6 months
Secondary	Whole Blood Red Blood Cell Count	Change from baseline in fasting whole blood red blood cell count (x10^6/uL)	6 months
Secondary	Whole Blood Red Blood Cell Distribution Width	Change from baseline in fasting whole blood red blood cell distribution width (%)	6 months
Secondary	Whole Blood Mean Corpuscular Volume	Change from baseline in fasting whole blood mean corpuscular volume (fL)	6 months
Secondary	Whole Blood Mean Corpuscular Hemoglobin	Change from baseline in fasting whole blood mean corpuscular hemoglobin (pg)	6 months
Secondary	Whole Blood Mean Corpuscular Hemoglobin Concentration	Change from baseline in fasting whole blood mean corpuscular hemoglobin concentration (g/dL)	6 months
Secondary	Whole Blood White Blood Cells	Change from baseline in fasting whole blood white blood cells (x10^3/uL)	6 months
Secondary	Whole Blood Neutrophils	Change from baseline in fasting whole blood neutrophils (cells/uL)	6 months
Secondary	Whole Blood Basophils	Change from baseline in fasting whole blood basophils (cells/uL)	6 months
Secondary	Whole Blood Eosinophils	Change from baseline in fasting whole blood eosinophils (cells/uL)	6 months
Secondary	Whole Blood Lymphocytes	Change from baseline in fasting whole blood lymphocytes (cells/uL)	6 months
Secondary	Whole Blood Monocytes	Change from baseline in fasting whole blood monocytes (cells/uL)	6 months
Secondary	Whole Blood Mean Platelet Volume	Change from baseline in fasting whole blood mean platelet volume (fL)	6 months
Secondary	Whole Blood Platelet Count	Change from baseline in fasting whole blood platelet count (x10^9/L)	6 months
Secondary	Serum Creatinine	Change from baseline in fasting serum creatinine (umol/L)	6 months
Secondary	Serum Blood Urea Nitrogen	Change from baseline in fasting serum blood urea nitrogen (mg/dL)	6 months
Secondary	Serum Alkaline Phosphatase (ALP)	Change from baseline in fasting serum ALP (U/L)	6 months
Secondary	Serum Asparatate Transaminase (AST)	Change from baseline in fasting serum AST (U/L)	6 months
Secondary	Serum Alanine Transaminase (ALT)	Change from baseline in fasting serum ALT (U/L)	6 months
Secondary	Serum Albumin	Change from baseline in fasting serum albumin (g/dL)	6 months
Secondary	Serum Total Protein	Change from baseline in fasting serum total protein (g/dL)	6 months
Secondary	Serum Chloride	Change from baseline in fasting serum chloride (mmol/L)	6 months
Secondary	Serum Sodium	Change from baseline in fasting serum sodium (mmol/L)	6 months
Secondary	Serum Potassium	Change from baseline in fasting serum potassium (mmol/L)	6 months
Secondary	Serum Calcium	Change from baseline in fasting serum calcium (mg/dL)	6 months
Secondary	Serum Urea	Change from baseline in fasting serum urea (mg/dL)	6 months
Secondary	Incidence of Adverse Events	Number of participants with adverse events	6 months