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Explorations Into the Mechanism for INSTI-associated Weight Gain: a Focus on Energy Balance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04495348
Recruitment Status : Recruiting
First Posted : July 31, 2020
Last Update Posted : November 4, 2020
Gilead Sciences
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:

Weight gain following antiretroviral therapy (ART) initiation occurs with all modern regimens. Recent real-world reports suggest that integrase strand transfer inhibitor (INSTI)-based ART may be associated with excess weight gain compared to other regimens. Weight gain appears to occur regardless of baseline weight, and is most pronounced among women and minorities, often those at highest risk of obesity-associated comorbidities. INSTI- and TAF-based regimens are now preferred regimens for most persons according to the Department of Health and Human Services ART-Treatment Guidelines. As a result, there is an urgent need to understand the underlying mechanisms for this weight gain.

This study aims to understand the changes in energy balance that occur with changes in ART. Participants with HIV who have experienced >10% weight gain on INSTI (bictegravir or dolutegravir-based therapy) will be switched to doravirine for 12 weeks, and then back to their prior INSTI regimen, allowing for assessment of changes in metabolic parameters with drug withdrawal and reintroduction (with no change to NRTI-backbone). Twenty-four hour energy balance will be measured on both regimens during a 24-hour stay using a whole room indirect calorimetry, with a standardized diet. Ultimately, the investigator's goal is to understand the mechanisms of weight gain so that future interventions can most effectively mitigate ART-associated weight changes.

Condition or disease Intervention/treatment
HIV-1-infection Weight Gain Drug: Doravirine

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Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Explorations Into the Mechanism for INSTI-associated Weight Gain: a Focus on Energy Balance
Actual Study Start Date : October 22, 2020
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : September 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Body Weight

Group/Cohort Intervention/treatment
Open-label arm
Participants are switched to doravirine and then switched back to INSTI-based therapy.
Drug: Doravirine
Participants will be switched to doravirine and then switched back to INSTI-based therapy to determine the impact on energy balance.

Primary Outcome Measures :
  1. Change in energy balance [ Time Frame: 24 weeks ]
    Change in total energy expenditure (kcal/day)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Participants with HIV who have experienced >10% weight gain on INSTI (bictegravir or dolutegravir-based therapy).

Inclusion Criteria:

  • Adults age >=18 years
  • BMI of >=30.0 kg/m2
  • >=10% weight gain within the first 2 years of switching to INSTI-based ART (bictegravir or dolutegravir-based regimens only), with weight gain that has continued or worsened (not decreased).
  • At least one plasma HIV-1 RNA <50 copies/mL while on the current INSTI-based ART within 6 months of screening
  • Willing to switch to doravirine and pay any associated co-pays that may not be covered by insurance.
  • NRTI back-bone therapy with either TAF or TDF with 3TC or FTC and willing to continue these 2 agents

Exclusion Criteria:

  • Use of an INSTI other than bictegravir or dolutegravir within the 1 year prior to entry
  • Any plasma HIV-1 RNA >500 copies/mL within one year prior to entry
  • Pregnant, breast-feeding, or intention to become pregnant during the study period.
  • Participants using medications with a potential serious drug-drug interaction with doravirine that cannot be attenuated through dose change will also be excluded.
  • Any plans to change diet or exercise regimen significantly within the study period.

NOTE: Significantly refers to intent to join a weight-loss program such as Weight Watchers, start a specific diet (such as ketogenic or very low carbohydrate).

- Use of human growth hormone, tesamorelin, supra-physiologic testosterone to achieve therapeutic blood levels, or any use of other anabolic steroids within 3 months prior to study entry or plans to start these on study.

NOTE: Chronic, stable hormone replacement therapy ≥3 months prior to entry in men with diagnosed hypogonadism or transgender person on masculinizing hormonal therapy is permitted.

- Use of estrogens or progesterones at supraphysiologic doses within 3 months prior to study entry.

NOTE: Stable doses used for contraception, post-menopausal hormone replacement or feminizing hormone therapy for transgender persons ≥3 months prior to entry is permitted.

  • Use of prednisone (or equivalent steroid) within the prior 3 months, unless stable dosing ≤ 10mg
  • Change or initiation of lipid- and/or glucose-lowering therapy in the 12 weeks prior to entry, or planned need for such therapy during the study period. Use of stable lipid- and/or glucose-lowering therapy during the study is allowed.
  • Current serious illness requiring systemic treatment and/or hospitalization until participant completes therapy or is clinically stable as determined by the site investigator.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Intent to use any medication likely to cause significant changes in weight during the study period.

NOTE: A list of medications in this category will be provided.

  • Prior bariatric surgery (e.g., lap band, gastric sleeve, or roux-en-y bypass surgery) or major gastric surgery or plans to undergo weight reduction surgery while on study.
  • Screening laboratory values as follows:

ANC < 500 cells/mm3 Hemoglobin < 9 gm/dL Cr Cl < 30 mL/min (estimated by CKD-Epi equation) Fasting blood sugar <200

  • Any chronic, end-stage organ disease that would impact metabolism, including end-stage liver or renal disease, cardiac cachexia, chronic obstructive pulmonary disease, or cancer
  • Any condition that the study investigator believes would make the candidate unsuitable for participation.
  • Severe claustrophobia that would limit ability of participant to remain in the whole room calorimeter
  • Known resistance to any component of the study drugs, including detection of any of the following resistance mutations on prior HIV genotype test (genotype testing not required if not available): Doravirine resistance: V106A, V106I, V106T, V106M, Y188C, Y188H, Y188L, G190E, P225H, F227C, F227L, F227R, M230L, L234I Resistance to NRTIs: K65R, K65E, K65N, T69S (insertion complex), K70E, L74V, Y115F, Q151M, M184I, M184V.
  • Active severe depression or anxiety, as evidenced by recent inpatient psychiatric admission (within the prior 6 months); PHQ-2 score of 6 (response of 'nearly every day' to 'do you have little interest or pleasure in doing things' or 'feeling down, depressed, or hopeless'; expressed suicidal ideations.
  • Under the care of a provider for disordered eating (bulimia, anorexia, or other).
  • Diabetes will be permitted if well-controlled with a Hb A1C of 7.5% of less in the prior 6 months and no use of insulin.
  • Routine physical activity meeting or exceeding 150 minutes/week of moderate or vigorous activity, for at least 3 months prior to the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04495348

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Contact: Kristine Erlandson, MD 303-724-4941
Contact: Suzanne Fiorillo 303-724-5931

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United States, Colorado
University of Colorado Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Kristine Erlandson, MD    303-724-4941   
United States, Texas
UTHealth Not yet recruiting
Houston, Texas, United States, 77030
Contact: Jordan Lake, MD    713-500-6767   
Sponsors and Collaborators
University of Colorado, Denver
Gilead Sciences
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Principal Investigator: Kristine Erlandson, MD University of Colorado Denver, Anschutz Medical Campus
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Responsible Party: University of Colorado, Denver Identifier: NCT04495348    
Other Study ID Numbers: 19-2960
First Posted: July 31, 2020    Key Record Dates
Last Update Posted: November 4, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: No
Additional relevant MeSH terms:
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Body Weight
Weight Gain
Body Weight Changes