Expression of Longevity Genes in Response to Extended Fasting

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01059760

Acronym

FEELGOOD

Enrollment

Registered

2010-02-01

Start date

2010-01-31

Completion date

2010-10-31

Last updated

2017-07-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiovascular Disease

Keywords

Fasting, Short-term starvation, Diet, Coronary artery disease

Brief summary

The purpose of this study is to evaluate the effect of fasting on physical changes associated with cardiovascular disease.

Detailed description

Coronary heart disease (CHD) is the largest contributor to morbidity and mortality in the Western world and is associated with high-calorie diet, high body mass, and a variety of other factors. CHD can lead to myocardial infarction (MI) and other embolic events. A growing body of evidence suggests that relatively low caloric intake in the diets of a variety of animals increases longevity and preliminary evidence among humans indicates that such caloric restriction reduces risk factors for CHD, including cholesterol levels, blood pressure, glucose, and obesity. Caloric restriction has also been shown to alter the expression of certain genes, especially the forkhead box (FOX) O and sirtuin (SIRT) genes whose over-expression has been shown to increase longevity in animal models. Extended avoidance of caloric intake, also called fasting or short-term starvation, has been shown to increase expression of the FOXA genes that have similar sequence and function as the FOXO genes and that have been shown to increase longevity among animals regardless of FOXO function. We recently demonstrated that the risk of CHD was significantly lower among patients who reported a history of routine periodic extended fasting. The two primary hypotheses for this observation are that fasting may improve individual ability to control dietary intake or that fasting may initiate a cascade of protective mechanisms that preserve cellular and metabolic health.

Interventions

BEHAVIORALFasting First

28±4 hours of water-only fasting followed by 28±4 hours fed

BEHAVIORALFed First

28± 4 hours fed followed by 28± 4 hours of fasting

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Yes

Inclusion criteria

1. The volunteer (male or non-pregnant female, any ethnicity) must be \>18 years of age. 2. The volunteer must either have a body mass index of 25.0-35.0 kg/m2 or the combination of a body mass index of 18.5-24.9 kg/m2 and two or more previously or currently measured symptoms of the metabolic syndrome (fasting glucose≥110 mg/dL, triglycerides≥150 mg/dL, high-density lipoprotein cholesterol\<40 mg/dL in males or \<50 mg/dL in females, systolic blood pressure≥130 mmHg or diastolic blood pressure≥85 mmHg, or waist circumference≥40 inches in males or ≥36 inches in females \[glucose and cholesterol levels may be self-reported\]). 3. The volunteer has not routinely participated in caloric restriction (deliberate limitation of caloric intake of \<80% than the FDA-recommended daily caloric intake) within the last 2 years, has not participated in extended fasting (\>12 hours at a time) for at least a year, and does not deliberately skip meals as a routine dietary practice.

Exclusion criteria

1. Body mass index \<18.5 or \>35 kg/m2. 2. Current active cancer treatment, treatment with immunosuppressive medications, or solid organ transplantation within 1 year. 3. Presence of immunosuppressive disease, myocardial infarction, peripheral vascular disease, or stroke within the past year. 4. Use of insulin. 5. Although it is unlikely fasting will harm the pregnant or lactating woman, the dietary restrictions placed on the participant for the duration of the study may conflict with dietary recommendations for pregnant or lactating women. Women of child bearing potential, therefore, will meet an exclusion if they become pregnant.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Participant Glucose When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Human Growth Hormone (HGH) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Insulin When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) When Fasting and Fed	Baseline and 3 days	HOMA-IR is used to measure the severity of insulin resistance. Healthy Range: 1.0 (0.5-1.4) Less than 1.0 is optimal Above 1.9 indicates early insulin resistance Above 2.9 indicates significant insulin resistance
Change From Baseline in Participant Glycogen-Like Protein-1 (GLP-1) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Adiponectin When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Fibroblast Growth Factor-21 (FGF-21) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant White Blood Cell Count (WBC) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Hemoglobin When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Red Blood Cell Count (RBC) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Hematocrit When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Platelet Count When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Mean Corpuscular Volume (MCV) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Mean Corpuscular Hemoglobin (MCH) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Mean Corpuscular Hemoglobin Concentration (MCHC) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Red Cell Distribution Width (RDW) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Mean Platelet Volume (MPV) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Bicarbonate When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Sodium When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Chloride When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Blood Urea Nitrogen (BUN) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Calcium When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Potassium When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Creatinine When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Total Cholesterol (TC) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Low-Density Lipoprotein Cholesterol (LDL-C) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant High-Density Lipoprotein Cholesterol (HDL-C) When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Triglycerides When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant TC/HDL Ratio When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Weight When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Waist Circumference When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Systolic Blood Pressure (SBP), Supine When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant Diastolic Blood Pressure (DBP), Supine When Fasting and Fed	Baseline and 3 days	—
Change From Baseline in Participant High Sensitivity C-Reactive Protein (hsCRP) When Fasting and Fed	Baseline and 3 days	—

Countries

United States

Participant flow

Participants by arm

Arm	Count
Fasting Day First 28±4 hours of water-only fasting followed by 28±4 hours fed	16
Fed Day First 28± 4 hours fed followed by 28± 4 hours of fasting	14
Total	30

Baseline characteristics

Characteristic	Fed Day First	Total	Fasting Day First
Age, Continuous	44.0 years STANDARD_DEVIATION 14	43.6 years STANDARD_DEVIATION 13.5	43.3 years STANDARD_DEVIATION 13.6
Body Mass Index (BMI)	27.3 kg/m^2 STANDARD_DEVIATION 6.1	27.8 kg/m^2 STANDARD_DEVIATION 1.3	28.4 kg/m^2 STANDARD_DEVIATION 7.1
Hemoglobin A1C	5.3 percentage STANDARD_DEVIATION 0.3	5.4 percentage STANDARD_DEVIATION 0.3	5.5 percentage STANDARD_DEVIATION 0.3
Region of Enrollment United States	14 participants	30 participants	16 participants
Sex: Female, Male Female	9 Participants	20 Participants	11 Participants
Sex: Female, Male Male	5 Participants	10 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	2 / 16	1 / 14
serious Total, serious adverse events	0 / 16	0 / 14