Clinical trial NCT03489109: 2-5 Intermittent Caloric Restriction in HIV
Official title: 2-5 Intermittent Caloric Restriction for Weight Loss and Insulin Resistance in HIV-Infected Adults With Features of the Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Human Immunodeficiency Virus
Metabolic Syndrome
Keywords: Fasting
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2018-04-05
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background:

Weight gain can lead to obesity and diabetes even in people living with human immunodeficiency virus (HIV). Researchers want to see if the technique intermittent calorie restriction can help overweight people with HIV as an alternative to traditional diets.

Objective:

To see if intermittent calorie restriction leads to weight loss and improved blood sugar in obese people with HIV.

Eligibility:

Adults ages 18-65 with HIV who are obese and do not have diabetes

Design:

Participants will be screened with a medical history, physical exam, and blood and urine tests.

Before starting treatment, participants will:

* Have a nutritional consultation
* Get a pedometer to record daily steps
* Test a restricted diet for 1 day
* Have a body x-ray

At the baseline visit, participants will have:

* Blood drawn after they drink a sugar drink
* Questions about their health and eating
* A nutritional consultation
* Resting energy expenditure measured. Participants will fast overnight. Then they will lie down while a plastic bubble goes over the head and a plastic sheet covers the upper body. Oxygen flows into the bubble.
* Liver stiffness test. A wand on the stomach releases sound waves like an ultrasound.

For 12 weeks, some participants will be on a standard diet. Others will restrict how much food they eat 2 days a week. On those days they will eat about 25% of their recommended calories.

Participants will keep a diary of their diet and steps.

Participants will have 4 visits during the 12-week diet and 1 visit 12 weeks after the diet ends. They will repeat previous tests.

Detailed description: The high prevalence of obesity coupled with chronic inflammation and immune activation places human immunodeficiency virus (HIV)-infected individuals at increased risk for metabolic complications emphasizing the need for more aggressive management of obesity and related co-morbidities in the aging HIV-infected population. The most effective treatment for obesity and metabolic syndrome is lifestyle modification, usually with a combination of caloric restriction and increased exercise. Intermittent caloric restriction (ICR) or intermittent fasting simplifies caloric restriction by severely limiting calories only a few days per week and allowing ad lib diet on the other days. Weight loss benefits are similar to those seen with conventional diets, however, data suggests possible added health benefits from intermittent fasting.

We propose to study the benefits of a 2-5 ICR strategy on weight, insulin resistance, and cardiovascular disease markers in obese HIV-infected adults with features of the metabolic syndrome. In a prospective pilot study, 50 HIVinfected adults will be randomized 1:1 to ICR or standard-of-care instruction of healthy diet and lifestyle for a 12-week intervention period. We hypothesize that ICR (2 days per week) will be an effective and acceptable diet strategy that will result in significant weight reduction, improvements in insulin sensitivity, and related metabolic parameters.

Eligibility criteria: -INCLUSION CRITERIA:

1. Aged 18 to 65 years
2. HIV RNA level less than or equal to 200 copies/mL for greater than or equal to1 year (1 measure greater than or equal to 200 allowed if also \<500 and preceded and followed by one or more undetectable values)
3. Cluster of differentiation 4 (CD4) \>200 cells/mL and no active opportunistic infection or malignancy
4. BMI greater than or equal to 30 kg/m\^2
5. One or more components of the metabolic syndrome as defined below.

   * Risk Factor: Waist circumference

     * Men: Defining Level: \>102 cm
     * Women: Defining Level: \>88 cm
   * Risk Factor: Triglycerides, greater than or equal to 150 mg/dL
   * Risk Factor: High density lipoprotein (HDL) cholesterol

     * Men: Defining Level: \<40 mg/dL
     * Women: Defining Level: \<50 mg/dL
   * Risk Factor: Blood pressure, greater than or equal to 130 / greater than or equal to 85 mmHg
   * Risk Factor: Fasting glucose, greater than or equal to 110 mg/dL
6. Fasting blood glucose \>60 mg/dL at screening
7. Willingness to allow sample storage for future research
8. Able to provide informed consent

EXCLUSION CRITERIA:

1. Established diagnosis of diabetes mellitus use of anti-diabetes medications, or a hemoglobin A1C (HgbA1C) of \>7.0%
2. History of eating disorder, uncontrolled mood or thought disorder, significant gastrointestinal disorder or malabsorption, or significant hepatic or renal impairment
3. Current use of medical therapy for overweight/obesity including phentermine, orlistat, lorcaserin, naltrexone/bupropion, and liraglutide or history of weight loss surgery. Concomitant use of medications with side effects known to potentially influence appetite are allowed if on a stable dose for at least 12 months
4. History of symptomatic hypoglycemia.
5. Use of systemic glucocorticoids (stable dose daily inhaled corticosteroid allowed)
6. Chronic viral hepatitis C; subjects with a history of hepatitis C successfully treated can enroll \>12 months after sustained virologic response
7. Alcohol or substance use disorder in the past year as defined by Diagnostic and Statistical Manual (DSM)-V or positive urine drug screen
8. Current pregnancy, actively seeking to become pregnant or breastfeeding
9. Any serious health or other condition which, in the opinion of the PI or their designee, could potentially interfere with the ability of a subject to comply with the procedures and assessments of the protocol or to safely participate and complete the study.

Primary outcomes:
measure: Change in Weight
timeFrame: Assessed before 12-week intervention (baseline) and at week 12
measure: Change in Insulin Sensitivity
timeFrame: Assessed before 12-week intervention (baseline) and at week 12
Secondary outcomes:
measure: Change in Controlled Attenuation Parameter (CAP) Score
timeFrame: Assessed before 12-week intervention (baseline) and at week 12
measure: Change in Visceral Adipose Tissue
timeFrame: Assessed before 12-week intervention (baseline) and at week 12
measure: Change in Lipid Panel Levels
timeFrame: Assessed before 12-week intervention (baseline) and at week 12
measure: Change in C-reactive Protein (CRP) Levels
timeFrame: Assessed before 12-week intervention (baseline) and at week 12
measure: Change in Beck Depression Inventory (BDI) Score
timeFrame: Assessed before 12-week intervention (baseline) and at week 12
measure: Self-reported Compliance Rate With Assigned Diet
timeFrame: Compliance reported at Week 12
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
name: Colleen M Hadigan, M.D.
role: PRINCIPAL_INVESTIGATOR
References: