Knee OsteoarthritisSTARTNCT01489462
Strength Training for ARthritis Trial
A study testing High Intensity Strength Training and Low Intensity Strength Training in people with Knee Osteoarthritis, run by Wake Forest University at 1 site in United States.
Trial summary
The primary purpose of this study is to compare the effects of a high and low intensity strength training programs vs. a control group on knee pain and compressive joint forces. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- High Intensity Strength Training and Low Intensity Strength Training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 377 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Aug 2018
- Phase
- Interventional
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Mild to Moderate Knee Osteoarthritis
Who cannot join
- BMI <20 kg/m2 and ≥45 kg/m2
- Knee varus malalignment
- Participation in formal strength training for more than 30 min/week in the past 6 months.
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University
Winston-Salem, North Carolina, 27109
About this study
The primary purpose of this study is to compare the effects of a high and low intensity strength training programs vs. a control group on knee pain and compressive joint forces.
Read the detailed description
Muscle loss and fat gain contribute to the disability, pain, and morbidity associated with knee osteoarthritis (OA), and thigh muscle weakness is an independent and modifiable risk factor for it. However, while all published treatment guidelines, supported by Level-1 evidence, recommend muscle strengthening to combat sarcopenia and improve muscle quality in knee OA patients, previous strength-training studies either used intensities or loads below recommended levels or were generally short, lasting only 6 to 24 weeks. Consequently, they had low-to-modest effect sizes, could not detect changes in disease progression, did not address underlying OA mechanisms, and provided little lasting clinical benefit. The positive effects of long-term, structured exercise are known to persist even years after supervised treatment terminates.
The efficacy of high intensity strength training in improving OA symptoms, slowing progression, and affecting the underlying mechanisms has not been examined due to the unsubstantiated belief that it might exacerbate symptoms. Our preliminary data clearly show excellent tolerance for high-intensity strength training as well as reduced pain and increased function among older adults with knee OA. Similar studies in healthy older adults found improvements in thigh muscle mass and decreases in thigh fat mass with minimal alteration in total body weight after 16-18 weeks of training. We now propose an 18-month, high-intensity strength-training intervention for older adults with knee OA, focused on improving thigh composition (more muscle and less fat). We hypothesize that in addition to short-term clinical benefits, combining greater duration with high intensity will alter thigh composition sufficiently to attain long-term changes in knee-joint forces, decrease inflammatory cytokines, lower pain levels, and slow OA progression, which has yet to be convincingly demonstrated for any OA treatment. These are important benefits that are not achievable with shorter interventions.
Participants will be randomized to one of 3 groups: high-intensity strength training; low-intensity strength training; or attention control. The primary clinical aim is to compare the interventions' effects on knee pain, and the primary mechanistic aim is to compare their effects on knee-joint compressive forces during walking, a mechanism that affects the OA disease pathway. Secondary aims will compare intervention effects on additional clinical measures of disease severity (e.g., function, mobility); disease progression, measured by xray; thigh muscle and fat volume, measured by CT; components of thigh muscle function, including hip abductor strength and quadriceps strength, power, and proprioception; additional measures of knee-joint loading; and inflammatory and OA biomarkers.
- Conditions
- Knee Osteoarthritis
- Being tested
- High Intensity Strength Training, Low Intensity Strength Training, Attention Control
- Keywords
- Arthritis, Osteoarthritis, Strength Training
- Medical subject headings
- Osteoarthritis, Knee, Arthritis, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Intensity Strength TrainingBehavioural
The strength-training intervention will consist of 5-min warm-up, 40-min training, and 15-min cool-down. The 60-min sessions will be conducted 3 times/wk for 18 months. Every 2 weeks the load lifted will be adjusted so that the participants in this group are lifting 3 sets of each exercise at 75-90% of 1RM.
Low Intensity Strength TrainingBehavioural
The strength-training intervention will consist of 5-min warm-up, 40-min training, and 15-min cool-down. The 60-min sessions will be conducted 3 times/wk for 18 months. Every 2 weeks the load lifted will be adjusted so that the participants are lifting 3 sets of 15 repetitions at 30-40% of 1RM.
Attention ControlBehavioural
Participants in the control group will attend 60-min organized workshops 2 times/month for the first 6 months and then 1 time/month for months 7-18. Over the 18 months interactive presentations will cover such topics as foot care, nutrition, managing medication, and sleep practices, and experts will give wide-ranging lectures.
| Study group | Role | What they receive |
|---|---|---|
| High Intensity Strength Training | Experimental | The strength-training intervention will consist of 5-min warm-up, 40-min training, and 15-min cool-down. The 60-min sessions will be conducted 3 times/wk for 18 months. Every 2 weeks the load lifted will be adjusted so that the participants in this group are lifting 3 sets of each exercise at 75-90% of 1RM. Receives: Behavioral: High Intensity Strength Training |
| Low Intensity Strength Training | Experimental | The strength-training intervention will consist of 5-min warm-up, 40-min training, and 15-min cool-down. The 60-min sessions will be conducted 3 times/wk for 18 months. Every 2 weeks the load lifted will be adjusted so that the participants are lifting 3 sets of 15 repetitions at 30-40% of 1RM. Receives: Behavioral: Low Intensity Strength Training |
| Attention Control | Active comparator | Participants in the control group will attend 60-min organized workshops 2 times/month for the first 6 months and then 1 time/month for months 7-18. Over the 18 months interactive presentations will cover such topics as foot care, nutrition, managing medication, and sleep practices, and experts will give wide-ranging lectures. Receives: Behavioral: Attention Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
WOMAC Pain
To determine if an 18-month, high-intensity strength-training intervention significantly decreases pain relative to low-intensity strength training and attention control groups. The pain index assesses participants' pain on a scale, ranging from 0 (none) to 4 (extreme). The pain subscale consists of 5 items and total scores can range from 0-20, with larger scores indicating greater pain.
Measured: Baseline, 18 months
Knee Compressive Forces
To compare the effects of 18 months of high-intensity strength training, low-intensity strength training, and attention control on knee-joint compressive forces during walking.
Measured: Baseline, 18 Months
Secondary outcomes (10)
WOMAC Pain
To determine if 6 months of high-intensity strength training reduces pain significantly more than 6 months of low-intensity strength training or an attention control. The pain index assesses participants' pain on a scale, ranging from 0 (none) to 4 (extreme). The pain subscale consists of 5 items and total scores can range from 0-20, with larger scores indicating greater pain.
Measured: Baseline, 6 months
WOMAC Function
To determine if 6 months of high-intensity strength training improves function significantly more than 6 months of low-intensity strength training or an attention control. The LK version asks participants to indicate on a scale from 0 (none) to 4 (extreme) the degree of difficulty experienced in the last week due to knee OA. Individual scores for the 17 items are totaled to generate a summary score that could range from 0-68, with higher scores indicating poorer function.
Measured: Baseline, 6 months
Mobility
To determine if 6 months of high-intensity strength training improves mobility significantly more than 6 months of low-intensity strength training or an attention control. Participants are told to walk as far as possible in 6 minutes on an established course.
Measured: Baseline, 6 months
Knee Compressive Forces
To determine if 6 months of high-intensity strength training reduces knee-joint compressive loads significantly more than 6 months of low-intensity strength training or an attention control.
Measured: Baseline, 6 months
WOMAC Function
To compare the long-term effects of a high-intensity strength training, low-intensity strength training, and attention control group on function (clinical outcome). The LK version asks participants to indicate on a scale from 0 (none) to 4 (extreme) the degree of difficulty experienced in the last week due to knee OA. Individual scores for the 17 items are totaled to generate a summary score that could range from 0-68, with higher scores indicating poorer function.
Measured: Baseline, 18 Months
Mobility
To compare the long-term effects of a high-intensity strength training, low-intensity strength training, and attention control group on mobility (clinical outcome). Participants are told to walk as far as possible in 6 minutes on an established course.
Measured: Baseline, 18 Months
Knee Joint Loads
To compare the long-term effects of a high-intensity strength training, low-intensity strength training, and attention control group on knee joint loads (knee adductor moment, knee AP shear force) (mechanistic outcome).
Measured: Baseline, 18 Months
Structural Outcomes
To compare the effects of 18-month, high-intensity strength training, low-intensity strength training, and attention control on OA progression by changes in x-ray (e.g., joint space width).
Measured: Baseline, 18 Months
Thigh Composition & Muscle Function
To compare the effects on thigh muscle and fat volume of 18-month, high-intensity strength training, low-intensity strength training, and an attention control. To compare the effects of the interventions on components of muscle function, including hip abductor and quadriceps strength, and muscle power.
Measured: Baseline, 18 Months
Inflammatory & OA Markers
To compare the effects of the interventions on inflammation markers (IL-6, TNFα, sTNFR1, leptin) and OA biomarkers (serum PIIANP, COMP, urinary levels of CTX-II).
Measured: Baseline, 6 Months, 18 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2011 (estimated)
- Study startMar 2012
- Primary completionAug 2018
- Study completionAug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 377 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Sponsor
- Investigators
- Stephen P Messier, PhD, Principal investigator, Wake Forest University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01489462
- Sponsor's protocol ID
- R01AR059105
- Other IDs
- 1R01AR059105-01A1
- Acronym
- START
- Status last verified
- Oct 2017
- First submitted
- 22 Nov 2011
- Last updated
- 20 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Messier SP, Mihalko SL, Beavers DP, Nicklas BJ, DeVita P, Carr JJ, Hunter DJ, Lyles M, Guermazi A, Bennell KL, Loeser RF. Effect of High-Intensity Strength Training on Knee Pain and Knee Joint Compressive Forces Among Adults With Knee Osteoarthritis: The START Randomized Clinical Trial. JAMA. 2021 Feb 16;325(7):646-657. doi: 10.1001/jama.2021.0411.
PubMed 33591346Messier SP, Mihalko SL, Beavers DP, Nicklas BJ, DeVita P, Carr JJ, Hunter DJ, Williamson JD, Bennell KL, Guermazi A, Lyles M, Loeser RF. Strength Training for Arthritis Trial (START): design and rationale. BMC Musculoskelet Disord. 2013 Jul 15;14:208. doi: 10.1186/1471-2474-14-208.
PubMed 23855596
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Strength Training for ARthritis Trial
- ClinicalTrials.gov ID
- NCT01489462
- Acronym / sponsor ID
- START / R01AR059105
- Conditions
- Knee Osteoarthritis
- Keywords
- Arthritis, Osteoarthritis, Strength Training
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 377 participants (actual)
- Lead sponsor
- Wake Forest UniversityUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- Mar 2012
- Primary completion
- Aug 2018 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 9 Dec 2011 (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.
The primary purpose of this study is to compare the effects of a high and low intensity strength training programs vs. a control group on knee pain and compressive joint forces.
Detailed description
Muscle loss and fat gain contribute to the disability, pain, and morbidity associated with knee osteoarthritis (OA), and thigh muscle weakness is an independent and modifiable risk factor for it. However, while all published treatment guidelines, supported by Level-1 evidence, recommend muscle strengthening to combat sarcopenia and improve muscle quality in knee OA patients, previous strength-training studies either used intensities or loads below recommended levels or were generally short, lasting only 6 to 24 weeks. Consequently, they had low-to-modest effect sizes, could not detect changes in disease progression, did not address underlying OA mechanisms, and provided little lasting clinical benefit. The positive effects of long-term, structured exercise are known to persist even years after supervised treatment terminates.
The efficacy of high intensity strength training in improving OA symptoms, slowing progression, and affecting the underlying mechanisms has not been examined due to the unsubstantiated belief that it might exacerbate symptoms. Our preliminary data clearly show excellent tolerance for high-intensity strength training as well as reduced pain and increased function among older adults with knee OA. Similar studies in healthy older adults found improvements in thigh muscle mass and decreases in thigh fat mass with minimal alteration in total body weight after 16-18 weeks of training. We now propose an 18-month, high-intensity strength-training intervention for older adults with knee OA, focused on improving thigh composition (more muscle and less fat). We hypothesize that in addition to short-term clinical benefits, combining greater duration with high intensity will alter thigh composition sufficiently to attain long-term changes in knee-joint forces, decrease inflammatory cytokines, lower pain levels, and slow OA progression, which has yet to be convincingly demonstrated for any OA treatment. These are important benefits that are not achievable with shorter interventions.
Participants will be randomized to one of 3 groups: high-intensity strength training; low-intensity strength training; or attention control. The primary clinical aim is to compare the interventions' effects on knee pain, and the primary mechanistic aim is to compare their effects on knee-joint compressive forces during walking, a mechanism that affects the OA disease pathway. Secondary aims will compare intervention effects on additional clinical measures of disease severity (e.g., function, mobility); disease progression, measured by xray; thigh muscle and fat volume, measured by CT; components of thigh muscle function, including hip abductor strength and quadriceps strength, power, and proprioception; additional measures of knee-joint loading; and inflammatory and OA biomarkers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| High Intensity Strength Training | Experimental | Behavioral: High Intensity Strength TrainingThe strength-training intervention will consist of 5-min warm-up, 40-min training, and 15-min cool-down. The 60-min sessions will be conducted 3 times/wk for 18 months. Every 2 weeks the load lifted will be adjusted so that the participants in this group are lifting 3 sets of each exercise at 75-90% of 1RM. |
| Low Intensity Strength Training | Experimental | Behavioral: Low Intensity Strength TrainingThe strength-training intervention will consist of 5-min warm-up, 40-min training, and 15-min cool-down. The 60-min sessions will be conducted 3 times/wk for 18 months. Every 2 weeks the load lifted will be adjusted so that the participants are lifting 3 sets of 15 repetitions at 30-40% of 1RM. |
| Attention Control | Active comparator | Behavioral: Attention ControlParticipants in the control group will attend 60-min organized workshops 2 times/month for the first 6 months and then 1 time/month for months 7-18. Over the 18 months interactive presentations will cover such topics as foot care, nutrition, managing medication, and sleep practices, and experts will give wide-ranging lectures. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Mild to Moderate Knee Osteoarthritis
Key exclusion criteria (3 listed)
- BMI <20 kg/m2 and ≥45 kg/m2
- Knee varus malalignment
- Participation in formal strength training for more than 30 min/week in the past 6 months.
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 |
|---|---|---|
| High Intensity Strength TrainingThe strength-training intervention will consist of 5-min warm-up, 40-min training, and 15-min cool-down. The 60-min sessions will be conducted 3 times/wk for 18 months. Every 2 weeks the load lifted will be adjusted so that the participants in this group are lifting 3 sets of each exercise at 75-90% of 1RM. | Behavioural | High Intensity Strength Training |
| Low Intensity Strength TrainingThe strength-training intervention will consist of 5-min warm-up, 40-min training, and 15-min cool-down. The 60-min sessions will be conducted 3 times/wk for 18 months. Every 2 weeks the load lifted will be adjusted so that the participants are lifting 3 sets of 15 repetitions at 30-40% of 1RM. | Behavioural | Low Intensity Strength Training |
| Attention ControlParticipants in the control group will attend 60-min organized workshops 2 times/month for the first 6 months and then 1 time/month for months 7-18. Over the 18 months interactive presentations will cover such topics as foot care, nutrition, managing medication, and sleep practices, and experts will give wide-ranging lectures. | Behavioural | Attention Control |
Primary outcome
WOMAC Pain
Time frame: Baseline, 18 months
To determine if an 18-month, high-intensity strength-training intervention significantly decreases pain relative to low-intensity strength training and attention control groups. The pain index assesses participants' pain on a scale, ranging from 0 (none) to 4 (extreme). The pain subscale consists of 5 items and total scores can range from 0-20, with larger scores indicating greater pain.
Knee Compressive Forces
Time frame: Baseline, 18 Months
To compare the effects of 18 months of high-intensity strength training, low-intensity strength training, and attention control on knee-joint compressive forces during walking.
10 secondary outcomes
WOMAC Pain
Time frame: Baseline, 6 months
WOMAC Function
Time frame: Baseline, 6 months
Mobility
Time frame: Baseline, 6 months
Knee Compressive Forces
Time frame: Baseline, 6 months
WOMAC Function
Time frame: Baseline, 18 Months
Mobility
Time frame: Baseline, 18 Months
Knee Joint Loads
Time frame: Baseline, 18 Months
Structural Outcomes
Time frame: Baseline, 18 Months
Thigh Composition & Muscle Function
Time frame: Baseline, 18 Months
Inflammatory & OA Markers
Time frame: Baseline, 6 Months, 18 Months
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 20 Apr 2020.
- Derived from this study: PubMed 33591346Messier SP, Mihalko SL, Beavers DP, Nicklas BJ, DeVita P, Carr JJ, Hunter DJ, Lyles M, Guermazi A, Bennell KL, Loeser RF. Effect of High-Intensity Strength Training on Knee Pain and Knee Joint Compressive Forces Among Adults With Knee Osteoarthritis: The START Randomized Clinical Trial. JAMA. 2021 Feb 16;325(7):646-657. doi: 10.1001/jama.2021.0411.
- Derived from this study: PubMed 23855596Messier SP, Mihalko SL, Beavers DP, Nicklas BJ, DeVita P, Carr JJ, Hunter DJ, Williamson JD, Bennell KL, Guermazi A, Lyles M, Loeser RF. Strength Training for Arthritis Trial (START): design and rationale. BMC Musculoskelet Disord. 2013 Jul 15;14:208. doi: 10.1186/1471-2474-14-208.
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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.
Stephen P Messier, PhD principal investigator
Wake Forest University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High Intensity Strength Training and Low Intensity Strength Training in people with Knee Osteoarthritis, run by Wake Forest 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 1 inclusion and 3 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 20 Apr 2020. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
WOMAC Pain (time frame: Baseline, 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01489462, which also lists 2 linked publications.
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 20 Apr 2020; AzTrials last refreshed its copy on 5 Nov 2026.