Clinical trial NCT02770313: Weekly ONe-Day WatER-only Fasting InterventionaL Trial for Low-Density Lipoprotein Cholesterol Reduction
Official title: Weekly ONe-Day WatER-only Fasting InterventionaL Trial for Low-Density Lipoprotein Cholesterol Reduction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intermittent Fasting
Lead sponsor: Intermountain Health Care, Inc.
Sponsor class: OTHER
First posted: 2016-05-12
Enrollment: 103
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The goal of this study is to determine how effective repeated fasting over 26 weeks (6 months) is at improving risk parameters that are surrogate endpoints for cardiovascular diseases, metabolic dysregulation and cognitive impairments.

Subjects will be randomized 1:1 to water-only fasting or to their ad libitum usual diet, with randomization performed within strata based on fasting history (≤180 hours or 181-720 hours of total fasting for \>12 consecutive hours per episode in the previous two years). Subjects will be assessed at 4, 13 and 26 weeks following randomization.


Eligibility criteria: Inclusion Criteria:

1. Male or non-pregnant female, 21-70 years of age,

   * who are not currently taking a statin medication,
   * who have either pre-diabetes (clinical diagnosis, hemoglobin A1c ≥5.6%, or untreated fasting glucose \> 100 mg/dL within 6 months of screening) and are not taking medications to control diabetes OR diagnosed, diet-controlled type 2 diabetes but do not require medications to control diabetes OR one or more of the components of the metabolic syndrome measured within 6 months of screening (other than fasting glucose level \>100 mg/dL, i.e.: 1. systolic blood pressure ≥130 mmHg, or diastolic ≥85 mmHg, or use of an antihypertensive medication, 2. high-density lipoprotein cholesterol \<40 mg/dL for males or \<50 mg/dL for females, 3. triglycerides ≥150 mg/dL or use of a non-statin triglyceride-lowering medication (e.g., fibrate, niacin), 4. waist circumference ≥40 inches (102 cm) for males or ≥35 inches (88 cm) for females, or body mass index \>25 kg/m2),
   * are 21-39 years of age with LDL-C (measured within six months of screening) of 90-189 mg/dL OR are 40-70 years of age with LDL-C of 90-159 mg/dL OR are 21-70 years of age with LDL-C of 90 mg/dL or greater who have tried statins and stopped due to intolerance to the medications or who have one or more contraindications to statins and thus cannot take them but meet other study inclusion and exclusion criteria.
2. Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of any study procedures.

Exclusion Criteria:

1. Pregnant and/or lactating women and women of child bearing potential who are not using acceptable means of contraception. Women who become pregnant after enrollment in the study will be withdrawn for the health of the mother and baby.
2. Individuals who have fasted more than 15 hours per episode more than once per month during the past two years (i.e., \>720 hours over two years), except for those who fast during multiple weeks once per year (e.g., Muslim, Baha'i) who will be allowed to begin participation starting at two weeks after their preferred annual period of fasting ends (e.g., Ramadan or the Baha'i fast) and ending at six months prior to the beginning of the next annual observance, as long as they do not fast routinely outside of the one annual period of fasting.
3. Refusal to drink water while fasting.
4. Prior diagnosis of a chronic disease (i.e., defined as symptomatic coronary artery disease, coronary revascularization, myocardial infarction, unstable angina, stroke, transient ischemic attack, pulmonary embolism, peripheral vascular thromboembolism, chronic kidney disease stage III or higher, chronic obstructive pulmonary disease, immunodeficiency, solid organ transplant, eating disorder, type I diabetes, dementia, traumatic brain injury including post-concussive syndrome, and cancer of any type within the last 5 years other than cancer of the skin excluding melanoma).
5. Pre-diabetics or diabetics on diabetes medication.
6. Participation in any other clinical trials involving investigational or marketed products within 30 days prior to entry in the study.
7. Other conditions that in the opinion of the Principal Investigator may increase risk to the subject and/or compromise the quality of the clinical trial.

Primary outcomes:
measure: Change score of low density lipoprotein cholesterol
timeFrame: 26 weeks
Secondary outcomes:
measure: Change score for Homeostatic Model Assessment - Insulin Resistance
timeFrame: 26 weeks
measure: Change score for Metabolic Syndrome Score
timeFrame: 26 weeks
measure: Change score for brain-derived neurotrophic factor (BDNF) level
timeFrame: 26 weeks
measure: Change score for the MicroCog test's general cognitive proficiency index score
timeFrame: 26 weeks
Other outcomes:
measure: Change score for gut microbiota composition based on 16S rDNA sequencing
timeFrame: 26 weeks
Locations:
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
Study officials:
affiliation: Intermountain Heart Institute
name: Benjamin D Horne, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bartholomew CL, Muhlestein JB, May HT, Le VT, Galenko O, Garrett KD, Brunker C, Hopkins RO, Carlquist JF, Knowlton KU, Anderson JL, Bailey BW, Horne BD. Randomized controlled trial of once-per-week intermittent fasting for health improvement: the WONDERFUL trial. Eur Heart J Open. 2021 Sep 3;1(2):oeab026. doi: 10.1093/ehjopen/oeab026. eCollection 2021 Sep.
citation: Horne BD, Anderson JL, May HT, Le VT, Galenko O, Drakos SG, Bair TL, Knowlton KU, Muhlestein JB. Intermittent fasting and changes in Galectin-3: A secondary analysis of a randomized controlled trial of disease-free subjects. Nutr Metab Cardiovasc Dis. 2022 Jun;32(6):1538-1548. doi: 10.1016/j.numecd.2022.03.001. Epub 2022 Mar 7.