Diet-induced Elevations in LDL-C and Progression of Atherosclerosis

NCT05733325 | Completed

• 1 other identifier: CSF-A1
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is an observational study examining the progression of subclinical coronary atherosclerosis in healthy participants who have an elevated LDL-C (above 190mg/dl) secondary to diet not associated with genetic familial hypercholesterolemia (FH). This study participants are classified to be Lean-Mass-Hyper-Responder (LMHR).

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Percent change in total non-calcified coronary plaque volume

  Percent change in total non-calcified coronary plaque volume from baseline (start of the study) till the final visit will be measured using Coronary Computed Tomography Angiography (CCTA).

  12 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Lean Mass Hyper-Responders: The target population are those who experience significant increases in LDL-C on VLC/KDs whilst also being healthy and relatively lean (BMI \<30mg/kg2 and waist circumference \<102 cm and 88 cm for men and women respectively if BMI 25-30 mg/kg2). These individuals are referred to as lean mass hyper-responders (LMHRs) with diet-induced hypercholesterolemia (DIH).

You may qualify if:

• Age ≥ 18 years old
• Had an LDL cholesterol of 160 mg/dL or below from most recent labs taken before adopting a low carb diet (requires documentary evidence)
• Has seen an increase of LDL cholesterol to 190 mg/dL or above from most recent labs on current diet \*\*
• Has LDL cholesterol levels at least 50% or greater compared to most recent documented value prior to starting the diet.
• On low carb, ketogenic diet for the last 24 months or more.
• HDL-C ≥ 60 mg/dL and triglyceride level ≤ 80 mg/dL \*\*
• Willingness to participate in the study and ability to sign informed consent
• In the investigator's opinion subjects are willing and likely able to comply with scheduled visits, laboratory tests, and other study procedures.
• Normal to low BP (systolic ≤ 130 mm Hg or diastolic ≤ 80 mm Hg) at screening/baseline (visit 1).
• Fasting glucose \< 110 mg/dL and HbA1c \< 6.0%) \*\*
• hsCRP \< 2 mg/L \*\*
• No prior diagnosis of Type 2 Diabetes
• No prior use of anti-diabetic medication
• Not currently taking lipid lowering supplements or medications including statins, red yeast rice, garlic, ezetimibe, berberine
• Requires documentary evidence

You may not qualify if:

• Untreated hypothyroidism (TSH \> 10)
• Use of medications that elevated LDL-C (anabolic steroids, isotretinoin, immunosuppressants, amiodarone, thiazide diuretics, glucocorticoids, or thiazolidinediones)
• Pregnancy
• Has smoked more than 100 cigarettes in lifetime
• An ongoing inflammatory disorder (e.g. psoriatic arthritis)
• History of atherosclerotic heart disease
• Known history of molecularly defined Familial Hypercholesterolemia
• BMI = or \> 30 kg/m\^2 (or waist circumference \> 88 cm or \> 102 cm for women and men respectively if BMI between 25-30 kg/m\^2)
• Renal insufficiency (calculated creatinine clearance of \<50 ml per minute, MDRD (modification of Diet in Renal Disease) equation).
• Use of Lipid lowering medication (Statins, etc) at the time of most recent labs taken before starting Ketogenic diet.
• AST (Aspartate aminotransferase) or ALT (Alanine Transaminase) \>2 times the upper limit of normal (ULN) at the Screening visit (V1), or a total bilirubin \>1.5 times the ULN unless the subject has a history of Gilbert's.
• Subject unable to provide medical records indicating lab results before starting a keto- diet.
• Subject has a history of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Note (1) A subject with a history of malignancy \>5 years prior to signing informed consent should have no evidence of residual or recurrent disease.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality at the Screening visit (V1) that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial.

Sponsors & Collaborators

• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: lead
• Citizen Science Foundation: collaborator

Study Sites (1)

Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center (The Lundquist Institute)

Torrance, California, 90502, United States

Location

Related Publications (1)

• Soto-Mota A, Norwitz NG, Manubolu VS, Kinninger A, Wood TR, Earls J, Feldman D, Budoff M. Longitudinal Data From the KETO-CTA Study: Plaque Predicts Plaque, ApoB Does Not. JACC Adv. 2025 Jul;4(7):101686. doi: 10.1016/j.jacadv.2025.101686. Epub 2025 Apr 7.

  PMID: 40192608 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Matthew A Budoff, MD

  The Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: February 17, 2023
• Study Start: October 18, 2021
• Primary Completion: February 12, 2024
• Study Completion: February 12, 2024
• Last Updated: March 19, 2024

Record last verified: 2024-03

Locations

US (1)