Rheumatoid ArthritisPhase 1NCT02535832
Skeletal Muscle Dysfunction in Rheumatoid Arthritis (RA)
A Phase 1 study testing Pioglitazone in people with Rheumatoid Arthritis and Insulin Resistance, run by Ohio State University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis, Insulin Resistance
- What is being tested?
- Pioglitazone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2015to Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
- Inclusion Criteria for RA patients who are: (i) insulin resistant by the 2-hour glucose tolerance test; (ii) have the presence of 3 or more risk factors for metabolic syndrome (MetS) according to the ATP III Clinical Identification of MetS criteria; (iii) have a Hemoglobin A1c level equal or greater than 5.7 and less than 6.5.
- 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
Who cannot join
- 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
- Exclusion criteria (pioglitazone randomized clinical trial):
- 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
Show all 14Show fewer
- 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.
- Exclusion criteria for the muscle biopsy (cross-sectional and pioglitazone randomized clinical trial):
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
The investigator plans to enroll 80 participants with RA and 30 non-RA controls between the ages of 35 and 65 between August 2015 and December 2018 (arm-1). The investigator plan to perform a needle muscle biopsy in a subset of participants who agree to undergo this procedure. From the total cohort number of enrolled participants, 36 participants will be identified as having insulin resistance and recruit them to participate in the pioglitazone study (arm-2). Those patients who elect to participate further in the pioglitazone/ placebo study will sign separate consent document during Visit 1.
Since RA is more common in women, it is anticipated that 2/3 of the participants will be women. Children, pregnant or breast-feeding women, adults with impaired consent capacity, or vulnerable populations will not be enrolled.
In the cross-sectional study, after having provided informed consent, participants will undergo a history and physical exam by a rheumatologist to verify diagnosis of RA or that they are a healthy volunteer. All inclusion and exclusion criteria will be verified by the examining physician. During this visit, the participants will complete questionnaires including the Brief Pain Inventory (BPI), Health Assessment Questionnaire (HAQ), Patient Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-36. Participants will undergo dual energy x-ray absorptiometry (DXA) scanning to assess muscle mass of the upper leg (dominant and non-dominant sides), as well as computed tomography (CT) to assess body composition. Women of child bearing age will undergo urine pregnancy testing. Participants will undergo strength testing and a fatiguing bout of knee extension exercise. Blood will be drawn for glucose, insulin, liver function tests (LFT), lipid profile, rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), insulin like growth factor (IGF-1), C-Reactive Protein (CRP), insulin like growth factor binding protein-1 (IGFBP-1) and insulin like growth factor binding protein-3 (IGFBP-3). All participants will be asked to wear an accelerometer for 7 day to measure physical activity. The participants will be scheduled to return to Center for Clinical and Translational Science (CCTS) within 7 days for biopsy of the vastus lateralis muscle.
In the pioglitazone clinical trial study, 36 participants who have insulin resistance will be recruited to receive pioglitazone. After the participants have provided informed consent, women of childbearing potential will be given a urine pregnancy test at visits 1, 3 and 6. The investigator will review participant eligibility and participants will be randomized to receive either pioglitazone 45 mg daily or matching placebo for 15 weeks. Below is the dosing schedule.
Participants will start by taking increasing doses for three weeks as follows: 1 capsule (15mg) 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 10 weeks of treatment. The placebo or non-pioglitazone capsules will look identical to the pioglitazone capsules, but will contain inert substances, and the escalating dose schedule will be the same.
If participants experience difficulty with the drug, the investigators will slow the pace of dose escalation. If they cannot take 45 mg/day, then they may be dropped from the study. The placebo capsules will look identical to the pioglitazone capsules, but will contain inert substances. Drug compounding and dispensing (including blinding) will be handled by the University of Kentucky's Investigational Drug Service, which routinely serves this function. All participants in the pioglitazone study will undergo a second round of assessments. During the 15-week drug trial, participants will receive monthly phone calls to monitor for adverse effects. Additionally, participants will be asked to fill out a daily medication diary to monitor compliance and adverse effects. A skeletal muscle biopsy will be performed after treatment with pioglitazone/ placebo, which will take place within 1-2 weeks after the second round of assessments following pioglitazone treatment.
- Conditions
- Rheumatoid Arthritis, Insulin Resistance
- Being tested
- Pioglitazone, Placebo
- Keywords
- Rheumatoid Arthritis
- Medical subject headings
- Arthritis, Rheumatoid, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos
Pioglitazone CT Scan DXA scan Needle muscle biopsy
PlaceboDrug
Placebo CT Scan DXA scan Needle muscle biopsy
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Pioglitazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity
2 hour oral glucose tolerance test will be performed after a 12-hour fast using 75 g glucose
Measured: 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)
Measured: Changes from baseline and 12 weeks
Monocytosis in peripheral blood
White blood cell populations will be isolated using flow cytometry.
Measured: Changes from baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2015 (estimated)
- Study startSep 2015
- Primary completionOct 2022
- Study completionOct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Beatriz Hanaoka, Ohio State University
- Investigators
- Beatriz Hanaoka, MD MPH, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02535832
- Sponsor's protocol ID
- 15-0585-F6A
- Status last verified
- Mar 2023
- First submitted
- 24 Aug 2015
- Last updated
- 27 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Skeletal Muscle Dysfunction in Rheumatoid Arthritis (RA)
- ClinicalTrials.gov ID
- NCT02535832
- Acronym / sponsor ID
- 15-0585-F6A
- Conditions
- Rheumatoid Arthritis, Insulin Resistance
- Keywords
- Rheumatoid Arthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Study start
- Sep 2015 (actual)
- Primary completion
- Oct 2022 (actual)
- Study completion
- Oct 2022 (actual)
- First posted
- 31 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The investigator plans to enroll 80 participants with RA and 30 non-RA controls between the ages of 35 and 65 between August 2015 and December 2018 (arm-1). The investigator plan to perform a needle muscle biopsy in a subset of participants who agree to undergo this procedure. From the total cohort number of enrolled participants, 36 participants will be identified as having insulin resistance and recruit them to participate in the pioglitazone study (arm-2). Those patients who elect to participate further in the pioglitazone/ placebo study will sign separate consent document during Visit 1.
Since RA is more common in women, it is anticipated that 2/3 of the participants will be women. Children, pregnant or breast-feeding women, adults with impaired consent capacity, or vulnerable populations will not be enrolled.
In the cross-sectional study, after having provided informed consent, participants will undergo a history and physical exam by a rheumatologist to verify diagnosis of RA or that they are a healthy volunteer. All inclusion and exclusion criteria will be verified by the examining physician. During this visit, the participants will complete questionnaires including the Brief Pain Inventory (BPI), Health Assessment Questionnaire (HAQ), Patient Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-36. Participants will undergo dual energy x-ray absorptiometry (DXA) scanning to assess muscle mass of the upper leg (dominant and non-dominant sides), as well as computed tomography (CT) to assess body composition. Women of child bearing age will undergo urine pregnancy testing. Participants will undergo strength testing and a fatiguing bout of knee extension exercise. Blood will be drawn for glucose, insulin, liver function tests (LFT), lipid profile, rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), insulin like growth factor (IGF-1), C-Reactive Protein (CRP), insulin like growth factor binding protein-1 (IGFBP-1) and insulin like growth factor binding protein-3 (IGFBP-3). All participants will be asked to wear an accelerometer for 7 day to measure physical activity. The participants will be scheduled to return to Center for Clinical and Translational Science (CCTS) within 7 days for biopsy of the vastus lateralis muscle.
In the pioglitazone clinical trial study, 36 participants who have insulin resistance will be recruited to receive pioglitazone. After the participants have provided informed consent, women of childbearing potential will be given a urine pregnancy test at visits 1, 3 and 6. The investigator will review participant eligibility and participants will be randomized to receive either pioglitazone 45 mg daily or matching placebo for 15 weeks. Below is the dosing schedule.
Participants will start by taking increasing doses for three weeks as follows: 1 capsule (15mg) 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 10 weeks of treatment. The placebo or non-pioglitazone capsules will look identical to the pioglitazone capsules, but will contain inert substances, and the escalating dose schedule will be the same.
If participants experience difficulty with the drug, the investigators will slow the pace of dose escalation. If they cannot take 45 mg/day, then they may be dropped from the study. The placebo capsules will look identical to the pioglitazone capsules, but will contain inert substances. Drug compounding and dispensing (including blinding) will be handled by the University of Kentucky's Investigational Drug Service, which routinely serves this function. All participants in the pioglitazone study will undergo a second round of assessments. During the 15-week drug trial, participants will receive monthly phone calls to monitor for adverse effects. Additionally, participants will be asked to fill out a daily medication diary to monitor compliance and adverse effects. A skeletal muscle biopsy will be performed after treatment with pioglitazone/ placebo, which will take place within 1-2 weeks after the second round of assessments following pioglitazone treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboFrom 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. |
| Pioglitazone | Active comparator | Drug: PioglitazoneFrom 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. |
Who may qualify
- Ages
- 35 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
- Inclusion Criteria for RA patients who are: (i) insulin resistant by the 2-hour glucose tolerance test; (ii) have the presence of 3 or more risk factors for metabolic syndrome (MetS) according to the ATP III Clinical Identification of MetS criteria; (iii) have a Hemoglobin A1c level equal or greater than 5.7 and less than 6.5.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PioglitazoneAlso: ActosPioglitazone CT Scan DXA scan Needle muscle biopsy | Drug | Pioglitazone |
| PlaceboPlacebo CT Scan DXA scan Needle muscle biopsy | Drug | Placebo |
Primary outcome
Insulin sensitivity
Time frame: Baseline
2 hour oral glucose tolerance test will be performed after a 12-hour fast using 75 g glucose
Skeletal muscle strength in the quadriceps muscle
Time frame: Changes from baseline and 12 weeks
isometric strength test of the lower-extremity muscles (with one leg extension) using a Biodex to measure maximum voluntary isometric contraction (MVIC)
Monocytosis in peripheral blood
Time frame: Changes from baseline and 12 weeks
White blood cell populations will be isolated using flow cytometry.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Beatriz Hanaoka, MD MPH principal investigator
Ohio State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pioglitazone in people with Rheumatoid Arthritis and Insulin Resistance, run by Ohio State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin sensitivity (time frame: Baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2023.