Skeletal Muscle Dysfunction in Rheumatoid Arthritis (RA)

NCT02535832 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 15-0585-F6A
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Muscle strength helps determine a person's quality of life and functional independence. Patients with rheumatoid arthritis often suffer from muscle weakness and a pre-diabetic condition called insulin resistance. By doing this study, the investigators hope to learn why patients with rheumatoid arthritis (RA) suffer from muscle weakness.

Conditions

Rheumatoid Arthritis; Insulin Resistance

Keywords

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

• Insulin sensitivity

  2 hour oral glucose tolerance test will be performed after a 12-hour fast using 75 g glucose

  Baseline

• Skeletal muscle strength in the quadriceps muscle

  isometric strength test of the lower-extremity muscles (with one leg extension) using a Biodex to measure maximum voluntary isometric contraction (MVIC)

  Changes from baseline and 12 weeks

• Monocytosis in peripheral blood

  White blood cell populations will be isolated using flow cytometry.

  Changes from baseline and 12 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

From the total participants enrolled into the cross-sectional study, the investigator will identify up to 18 participants who have insulin resistance and recruit them to participate in the placebo arm. Participants will take matching placebo throughout the 15 weeks of treatment.

Drug: Placebo

Pioglitazone

ACTIVE COMPARATOR

From the total participants enrolled into the cross-sectional study, the investigator will identify up to 18 participants who have insulin resistance and recruit them to participate in the pioglitazone arm. Participants will start by taking increasing doses for three weeks as follows: 1 capsule (15 mg) per day for 7 days, 1 capsule per day (30 mg) for 7 days, and 1 capsule (45mg), if tolerated. Participants will continue this dose (45 mg) throughout the 12 weeks of treatment.

Drug: Pioglitazone

Interventions

Pioglitazone DRUG

Pioglitazone CT Scan DXA scan Needle muscle biopsy

Also known as: Actos

Pioglitazone

Placebo DRUG

Placebo CT Scan DXA scan Needle muscle biopsy

Placebo

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 35-65
• Diagnosed with RA by a Rheumatologist and according to American College of Rheumatology 2010 criteria
• Age 35-65
• In generally good health
• Age 35-65
• Diagnosed with RA by a Rheumatologist and according to American College of Rheumatology 2010 criteria
• Insulin resistant according to the Matsuda index

You may not qualify if:

• Age \<35 or \>65
• Pregnant, breast-feeding, cognitive dysfunction, incarcerated or otherwise vulnerable persons
• Any acute or chronic medical or psychiatric disorder that, in the opinion of the investigators, would impair evaluation of the study measures
• Women of reproductive age who are pregnant or who do not agree to effective birth control or who are lactating
• Clinically significant hepatic, cardiac or renal impairment
• Untreated osteoporosis
• Active cancer other than skin cancer
• Use of drugs (other than glucocorticoids) or nutritional supplements known to affect skeletal muscle mass
• Participation in regular and intense physical training
• Severe edema.
• Bleeding diathesis or chronic anticoagulant therapy
• Unable or unwilling to discontinue aspirin or non-steroidal anti-inflammatory drugs for 5 days prior to muscle biopsy

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Insulin Resistance

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Beatriz Hanaoka, MD MPH

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 24, 2015
• First Posted: August 31, 2015
• Study Start: September 1, 2015
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: March 27, 2023

Record last verified: 2023-03

Locations

US (1)