α-ketoglutarate in Patients With Hypertension (AKGHTN)

The Effects of α-ketoglutarate on Blood Pressure and Endothelial Function in Hypertensive Patients

Cardiovascular and cerebrovascular diseases are most terrible killers endangering the health of Chinese residents, and hypertension is the most important risk factor. Hypertension related microvascular rarefaction and endothelial dysfunction are the common pathological basis and initiation of cardiovascular and cerebrovascular disease. Therefore, reducing blood pressure and delaying or reversing endothelial dysfunction is an effective way to treat hypertension and prevent cardiovascular disease. Alpha-ketoglutarate (αKG) is a critical metabolic intermediate in the tricarboxylic acid (TCA) cycle, involves in diverse cellular biological activities, such as central metabolism, antioxidative defense, epigenetic regulation, and cell proliferation. The latest research found that with the growth of age, the level of αKG is decreasing, and increasing the content of αKG can prolong the life of multiple species including human. Recent clinical trials found that αKG supplementation can effectively improve the level of αKG in cells, delay aging, improve the metabolic process of cells without adverse reactions. However, the effect of αKG supplementation on reducing blood pressure and protecting vascular endothelial function has not been reported. Therefore, this study aims to focus on hypertension, a major chronic disease, and to observe the effects of αKG supplementation on endothelial function and blood pressure in patients with hypertension, so as to provide a new treatment strategy for hypertension and associated endothelial dysfunction.

Study Overview

• Status: Recruiting
• Conditions: Hypertension
• Intervention / Treatment: Dietary supplement: Alpha-ketoglutarate supplied as 1000mg capsule; Behavioral: Behavioral: Lifestyle modification

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xia Wenhao, MD, PhD; Phone Number: +86 15818193120; Email: xiawhao@mail.sysu.cn
• Study Contact Backup: Name: Liu Zhefu; Phone Number: +86 18774082778; Email: liuzhf29@mail2.sysu.edu.cn

Study Locations

• China
  • Nanning
    • Guangxi, Nanning, China, 530028
      • Recruiting
      • Wenhao Xia
      • Contact: Xia Wenhao, MD,PhD; Phone Number: +8615818193120; Email: xiawhao@mail.sysu.edu.cn
      • Contact: Liu Zhefu; Phone Number: +8618774082778; Email: liuzhf29@mail2.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1、 Primary hypertension (office blood pressure: systolic blood pressure 130～159 mmHg and/or diastolic blood pressure 80～99 mmHg, which meets the diagnostic criteria of hypertension class 1 of 2018AHA hypertension guidelines) and accompanied by vascular dysfunction (FMD<5%); 2、 Age between 18 and 65 years old; 3, Not using any drugs and dietary supplements that affect blood pressure and vascular endothelial function in the last 3 months, mainly including antihypertensive, lipid-lowering, hypoglycemic drugs and natural plant extract antioxidants; 4、 Voluntarily sign the informed consent form after fully understanding the purpose and process of the study, disease characteristics, drug effects, methods of relevant examinations, and potential risks/benefits of the study.

Exclusion Criteria:

1. Presence of secondary hypertension (those who have been diagnosed with secondary hypertension in the past and have not been definitively cured, and if secondary hypertension is suspected, a complete examination is required to exclude common secondary hypertension, including renal hypertension (renal parenchymal lesions, renal artery stenosis), primary aldosteronism, Cushing's syndrome, pheochromocytoma, aortic constriction, and severe obstructive sleep apnea);
2. Acute myocardial infarction within the past 6 months;
3. recent history of stroke (within 6 months); 4, Dilated heart disease, hypertrophic cardiomyopathy, rheumatic heart disease, congenital heart disease, severe heart valve disease (severe valve stenosis and or regurgitation);

5. patients with a combination of serious physical illnesses, such as cancer; 6, Severe hepatic or renal dysfunction (ALT and or AST) ≥ 3 times the upper limit of normal, or dialysis end-stage renal disease or eGFR < 30 ml/min/1.73 m2, or serum creatinine > 2.5 mg/dL [> 221 μmol/L]); 7. Symptomatic heart failure or reduced left ventricular ejection fraction (<40%) within the past 6 months; 8. History of hypersensitivity to the study drug or to its components after administration; 9. Participating in other clinical studies; 10. Patients with mental illness who are unable to cooperate; 11, Pregnant, lactating or expectant mothers;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control group; Lifestyle modification only	Behavioral: Behavioral: Lifestyle modification; Lifestyle modification: intake 1400-1600 kcal/day: 54% carbohydrates, 24% proteins, 22% lipids, 108 mg cholesterol, 35 g fiber; avoid smoking and alcohol consumption; performing aerobic activity 4 days per week such as 45 min on a stationary bicycle.
Experimental: α-KG group; AKG Double Wood® + lifestyle modification	Dietary supplement: Alpha-ketoglutarate supplied as 1000mg capsule; AKG Double Wood® + lifestyle modification AKG Double Wood®: 500mg, qd, for one months. Lifestyle modification: intake 1400-1600 kcal/day: 54% carbohydrates, 24% proteins, 22% lipids, 108 mg cholesterol, 35 g fiber; avoid smoking and alcohol consumption; performing aerobic activity 4 days per week such as 45 min on a stationary bicycle.; Behavioral: Behavioral: Lifestyle modification; Lifestyle modification: intake 1400-1600 kcal/day: 54% carbohydrates, 24% proteins, 22% lipids, 108 mg cholesterol, 35 g fiber; avoid smoking and alcohol consumption; performing aerobic activity 4 days per week such as 45 min on a stationary bicycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of αKG on flow mediated dilation （FMD）	Change of FMD between αKG-treated participants and non-αKG-treated participants	Up to 1 month
Effect of αKG on brachial-ankle pulse wave velocity （baPWV）	Change of baPWV between αKG-treated participants and non-αKG-treated participants	Up to 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of αKG on blood pressure	Change of systolic blood pressure and diastolic blood pressure between αKG-treated participants and non-αKG-treated participants	Up to 1 month
Effect of αKG on serum αKG levels	Change of serum αKG levels between αKG-treated participants and non-αKG-treated participants	Up to 1 month
Effect of αKG on retinal vascular density	Change of retinal vascular density between αKG-treated participants and non-αKG-treated participants	Up to 1 month

Collaborators and Investigators

• Sponsor: Jun Tao
• Investigators: Study Chair: Xia Wenhao, MD, PhD, Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Estimated): May 30, 2024
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: May 31, 2024
• First Submitted That Met QC Criteria: May 31, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: May 31, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: KY-IIT-2024-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes