The ENRGISE (ENabling Reduction of Low-Grade Inflammation in SEniors) Pilot Study

NCT02676466 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB201500894 - A-NU01AG050499
• Study Type: interventional
• Target: 289
• Locations: 1 country
• Sites: 5

Brief Summary

ENRGISE Pilot Study will test the ability of anti-inflammatory interventions for preventing major mobility disability by improving or preserving walking ability.

Conditions

Inflammation

Keywords

Mobility

Outcome Measures

Primary Outcomes (2)

• Changes in the Interleukin-6 Level Between Groups

  Changes in the Interleukin-6 Level Between the Groups

  Changes from baseline to month 12

• Number of Participants Experiencing Major Mobility Disability

  The 400 meter walk test at usual pace is used to evaluate major mobility disability (MMD), defined as the inability to walk ¼ mile or 400 meters.

  12 months

Secondary Outcomes (5)

• Short Physical Performance Battery (SPPB)

  12 months

• Number of Participants Exhibiting Frailty

  12 months

• Isometric Hand Grip Strength

  12 months

• Peak Torque of the Knee Extensor and Flexor Muscles

  month 12

• Short Form Health Survey (SF-36) - Physical Component Score

  month 12

Study Arms (8)

Fish oil Active

EXPERIMENTAL

This group will receive the Omega-3 fish oil which will be administered at a dose of 1.4 grams per day for the first six months. Based on tolerability and inflammation level, dose may either continue at 1.4 grams per day or be increased to 2.8 grams per day for the remaining six month.

Dietary Supplement: Omega-3 fish oil

Fish oil Placebo

PLACEBO COMPARATOR

This group will receive a placebo which will be matching to the Omega-3 fish oil. The placebo corn oil are obtained in gel caps and they have identical shape, color, taste and weight. The doses will be administered at doses corresponding to the Omega-3 fish oil.

Other: Corn Oil (Fish oil Placebo)

Losartan Active

ACTIVE COMPARATOR

This group will receive the Losartan which will be administered at a starting dose of 25 milligrams per day. Based on tolerability, losartan will continue at a dose of either 25 milligrams per day or 50 milligrams per day for the first six months. Based on continued tolerability and inflammation level, dose may either continue at 25 or 50 milligrams per day or be increased to 100 milligrams per day for the remaining six months.

Drug: Losartan

Losartan Placebo

PLACEBO COMPARATOR

This group will receive a placebo which will be matching to the losartan. The placebo cellulose based capsule are obtained in 25 mg and 50 mg capsules. The shell capsules are cellulose based. Placebo and LO have identical shape, color, taste and weight. the doses will be administered at doses corresponding to the losartan.

Other: Cellulose Based (Losartan Placebo)

Fish oil Active + Losartan Active

ACTIVE COMPARATOR

This group will receive both the Losartan and Omega-3 fish oil. Losartan will be administered at a starting dose of 25 milligrams per day. Based on tolerability, losartan will continue at a dose of either 25 milligrams per day or 50 milligrams per day for the first six months. Based on continued tolerability and inflammation level, dose may either continue at 25 or 50 milligrams per day or be increased to 100 milligrams per day for the remaining six months. Omega-3 fish oil will be administered at a dose of 1.4 grams per day for the first six months. Based on tolerability and inflammation level, dose may either continue at 1.4 grams per day or be increased to 2.8 grams per day for the remaining six month.

Dietary Supplement: Omega-3 fish oil; Drug: Losartan

Fish oil Active + Losartan Placebo

OTHER

This group will receive the Omega-3 fish oil which will be administered at a dose of 1.4 grams per day for the first six months. Based on tolerability and inflammation level, dose may either continue at 1.4 grams per day or be increased to 2.8 grams per day for the remaining six month. In addition, this group will receive a placebo which will be matching to the losartan. The placebo cellulose based capsule are obtained in 25 mg and 50 mg capsules. The shell capsules are cellulose based. Placebo and LO have identical shape, color, taste and weight. the doses will be administered at doses corresponding to the losartan.

Dietary Supplement: Omega-3 fish oil; Other: Cellulose Based (Losartan Placebo)

Fish oil Placebo + Losartan Active

OTHER

This group will receive a placebo which will be matching to the Omega-3 fish oil. The placebo corn oil are obtained in gel caps and they have identical shape, color, taste and weight. The doses will be administered at doses corresponding to the Omega-3 fish oil. In addition, this group will receive the Losartan which will be administered at a starting dose of 25 milligrams per day. Based on tolerability, losartan will continue at a dose of either 25 milligrams per day or 50 milligrams per day for the first six months. Based on continued tolerability and inflammation level, dose may either continue at 25 or 50 milligrams per day or be increased to 100 milligrams per day for the remaining six months.

Drug: Losartan; Other: Corn Oil (Fish oil Placebo)

Fish oil Placebo + Losartan Placebo

OTHER

This group will receive a placebo which will be matching to both the omega-3 fish oil and losartan which will be administered at doses corresponding to doses administered for omega-3 fish oil and losartan throughout the 12 month study.

Other: Corn Oil (Fish oil Placebo); Other: Cellulose Based (Losartan Placebo)

Interventions

Omega-3 fish oil DIETARY_SUPPLEMENT

The Omega-3 fish oil will be provided in 700 mg gelcaps. The starting dose will be 1.4 g/day of fish oil and continue until the 6 month visit. If the average of IL-6 measured at 3- and 6-month visits does not decrease by \>40% vs. baseline (average of screening visits 1 and 2), we increase the dose to 2.8 g/day.

Fish oil Active; Fish oil Active + Losartan Active; Fish oil Active + Losartan Placebo

Losartan DRUG

The Losartan will be provided in 25 mg and 50 mg capsules. The starting dose will be 25 mg/day, if tolerated, then stepped up to 50 mg/day. If there are no safety concerns, a continuation of 50 mg/day will be provided until the 6 month visit. If the average of IL-6 measured at 3- and 6-month visits does not decrease by \>40% vs. baseline (average of screening visits 1 and 2), an increase to the dose of 100 mg/day.

Also known as: Cozaar

Fish oil Active + Losartan Active; Fish oil Placebo + Losartan Active; Losartan Active

Corn Oil (Fish oil Placebo) OTHER

The corn oil placebo gel caps will be identical in shape, color, taste and weight as the Omega-3 fish oil.

Also known as: Fish oil Placebo

Fish oil Placebo; Fish oil Placebo + Losartan Active; Fish oil Placebo + Losartan Placebo

Cellulose Based (Losartan Placebo) OTHER

The placebo cellulose based capsules will be identical in shape, color, taste and weight as the losartan capsules.

Also known as: Losartan Placebo

Fish oil Active + Losartan Placebo; Fish oil Placebo + Losartan Placebo; Losartan Placebo

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Men and women age \>70 years
• Self-reported difficulty walking ¼ of a mile or climbing a flight of stairs
• Walking speed \<1 meters per second and \>0.44 meters per second on the 4 meter walk at usual pace. A walking speed of \<0.44 meters per second would not be compatible with completing the 400 meter walk in 15 minutes. (In the pilot phase we explore the feasibility of recruiting at least 50% of participants who have a baseline walking speed of \<0.80 meters per second and \>0.44 meters per second)
• Able to complete the 400 meter walk test within 15 minutes without sitting or the help of another person and without a walker, a cane is allowed
• Blood level IL-6 \>2.5 pg/ml and \<30 pg/ml.
• Willingness to be randomized to the intervention groups

You may not qualify if:

• Failure or inability to provide informed consent
• Lives in a nursing home; persons living in assisted or independent housing are not excluded
• Self-reported inability to walk one block
• Significant cognitive impairment, defined as a known diagnosis of dementia, or a Mini-Mental State Exam (MMSE) score \<24 (\<23 for racial/ethnic minorities or participants with less than 9 years of education)
• Unable to communicate because of severe hearing loss or speech disorder
• Neurological conditions that are causing impaired muscle function or mobility (may include stroke with residual paresis, paralysis, neuropathy, Parkinson disease, or multiple sclerosis)
• Severe rheumatologic or orthopedic diseases, e.g., awaiting joint replacement, known active inflammatory or autoimmune disease (e.g. rheumatoid arthritis, lupus, Crohn's disease, HIV)
• Terminal illness with life expectancy less than 12 months
• Severe pulmonary disease, requiring either steroid pills or injections
• Other significant co-morbid disease that in the opinion of the field center PI would impair ability to participate in the trial, e.g. renal failure on hemodialysis, severe psychiatric disorder (e.g. bipolar, schizophrenia), excessive alcohol use (\>14 drinks per week); drug addiction; treatment for cancer (radiation or chemotherapy) within the past 1 year; or other conditions
• Lives outside of the study site or is planning to move out of the area in next 1 year or leave the area for \>3 months during the next year
• Intolerance or allergy to Angiotensin II Receptor Blockers (ARBs)
• Known bilateral renal artery stenosis or liver cirrhosis
• Hypotension Systolic Blood Pressure\<110 or Diastolic Blood Pressure\<60 mmHg
• Serum potassium ≥5.0 mEq/L

Sponsors & Collaborators

• University of Florida: lead
• National Institute on Aging (NIA): collaborator
• Abbott: collaborator

Study Sites (5)

University of Florida

Gainesville, Florida, 32611, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Tufts University

Boston, Massachusetts, 02111, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (2)

• Manini TM, Anton SD, Beavers DP, Cauley JA, Espeland MA, Fielding RA, Kritchevsky SB, Leeuwenburgh C, Lewis KH, Liu C, McDermott MM, Miller ME, Tracy RP, Walston JD, Radziszewska B, Lu J, Stowe C, Wu S, Newman AB, Ambrosius WT, Pahor M; ENRGISE Pilot study investigators. ENabling Reduction of Low-grade Inflammation in SEniors Pilot Study: Concept, Rationale, and Design. J Am Geriatr Soc. 2017 Sep;65(9):1961-1968. doi: 10.1111/jgs.14965. Epub 2017 Jul 22.

  PMID: 28734043 BACKGROUND

• Pahor M, Anton SD, Beavers DP, Cauley JA, Fielding RA, Kritchevsky SB, Leeuwenburgh C, Lewis KH, Liu CK, Lovato LC, Lu J, Manini TM, McDermott MM, Miller ME, Newman AB, Radziszewska B, Stowe CL, Tracy RP, Walkup MP, Wu SS, Ambrosius WT. Effect of Losartan and Fish Oil on Plasma IL-6 and Mobility in Older Persons. The ENRGISE Pilot Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci. 2019 Sep 15;74(10):1612-1619. doi: 10.1093/gerona/gly277.

  PMID: 30541065 DERIVED

MeSH Terms

Conditions

Inflammation

Interventions

Fish Oils; Losartan; Corn Oil

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Oils; Lipids; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Dietary Fats, Unsaturated; Dietary Fats; Fats; Fats, Unsaturated; Plant Oils; Plant Preparations; Biological Products; Complex Mixtures; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Results Point of Contact

• Title: ENRGISE Coordinating Center Project Manager
• Organization: University of Florida

ENGISEACC@aging.ufl.edu

352-294-5800

Study Officials

• Marco Pahor, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

• Walter Ambrosius, PhD

  Wake Forest University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2016
• First Posted: February 8, 2016
• Study Start: April 26, 2016
• Primary Completion: June 22, 2018
• Study Completion: June 22, 2018
• Last Updated: May 7, 2024
• Results First Posted: September 13, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: per NIH
• Access Criteria: per NIH

Locations

US (5)