Physical Therapy + Medication for Parkinson's Disease

(TAME-PD Trial)

Overseen By Jennifer Mule, B.S. Biology

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Hubert Fernandez

Must be taking: Dopaminergic therapy

Must not be taking: MAO inhibitors

Disqualifiers: Atypical parkinsonism, Epilepsy, Cardiac arrhythmia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: 12 weeks

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding medication to physical therapy can help people with Parkinson's disease improve walking and balance. Participants will receive either physical therapy alone or physical therapy combined with one of two medications: methylphenidate (a stimulant) or atomoxetine (a non-stimulant). The goal is to determine if the combined approach is more effective than physical therapy alone. Individuals with Parkinson's who experience significant walking or balance issues, have well-controlled symptoms with current medications, but still struggle, may be suitable for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that your medication regimen should be stable and unlikely to change in the next 30 days. If you are using MAO inhibitors, you must stop them at least two weeks before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that physical therapy is generally safe for people with Parkinson's disease, helping to manage symptoms and improve strength and balance. While some uncertainty about potential risks exists, physical therapy remains widely regarded as a safe treatment option.

When combined with the drug methylphenidate, studies suggest it is safe and effective for people with Parkinson's. Methylphenidate, also used for ADHD and narcolepsy, can aid with movement issues in Parkinson's. However, some individuals may experience side effects like trouble sleeping or a faster heartbeat.

For combining physical therapy with atomoxetine, most studies indicate it is well-tolerated by Parkinson's patients. Some might experience mild side effects like stomach upset or trouble sleeping, but these are not unexpected.

Overall, treatments that combine physical therapy with either methylphenidate or atomoxetine appear safe for Parkinson's patients, according to available research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of physical therapy with medications like methylphenidate and atomoxetine for Parkinson's disease because these treatments offer a fresh approach to managing symptoms. Unlike standard treatments that mainly involve dopamine replacement, methylphenidate and atomoxetine work by targeting norepinephrine pathways, potentially improving both motor and cognitive functions. Additionally, combining these medications with physical therapy could enhance overall movement and quality of life, offering a more holistic approach to care. This combination could address symptoms that existing therapies might not fully manage, providing renewed hope for improved patient outcomes.

What evidence suggests that this trial's treatments could be effective for improving gait and balance in Parkinson's disease?

Research has shown that physical therapy can greatly help people with Parkinson's disease by improving movement, walking, and balance. It enhances both mobility and stability, leading to better control. In this trial, one group of participants will receive only physical therapy.

Another group will receive physical therapy combined with Methylphenidate, a medication often used for attention and hyperactivity. This medication has been found to assist with thinking and movement issues in Parkinson's patients and may also boost attention, aiding movement.

A third group will receive physical therapy combined with Atomoxetine, a medication linked to better planning and multitasking abilities in people with Parkinson's. It might help improve brain functions related to movement control.

Combining these medications with physical therapy could further enhance walking and balance in those with Parkinson’s disease. ^{3 6 7 8 9}

Who Is on the Research Team?

Hubert Fernandez

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for Parkinson's disease patients with significant gait and balance issues, despite stable dopaminergic therapy. They must score ≥2 on the UPDRS item for walking impairment. Exclusions include severe mental health issues, epilepsy, heart problems, glaucoma, liver disease, allergies to study drugs, wheelchair dependence or bedridden state without help.

Inclusion Criteria

I have Parkinson's with major walking issues despite medication, not expected to change my meds soon.

Exclusion Criteria

I don't have conditions that majorly affect my walking or balance.

Previous deep brain stimulation procedure

I need help to move from a wheelchair or bed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive physical therapy sessions twice weekly for 12 weeks, with or without the addition of methylphenidate or atomoxetine

12 weeks

24 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atomoxetine
• Methylphenidate
• Physical Therapy

Trial Overview The TAME-PD trial is testing if adding low doses of either methylphenidate or atomoxetine to physical therapy can improve gait and balance in Parkinson's patients more than physical therapy alone. It's a pilot study where participants are randomly assigned to one of two groups in a blinded fashion.

How Is the Trial Designed?

Group I: Physical Therapy Active Control 1 Intervention

Physical Therapy (PT) will consist of two weekly sessions over a 12 week period using the Mellen center protocol PT for PD.

Group II: Physical Therapy plus Methylphenidate Active Control 2 Interventions

Methylphenidate 20 mg daily in combination with PT

Group III: Physical Therapy plus Atomoxetine Active Control 2 Interventions

Atomoxetine 10 mg daily in combination with PT or PT alone.

Who Is Running the Clinical Trial?

Hubert Fernandez

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

Research indicates that individuals with Parkinson's disease (PD) experience early signs of disability, including declines in gait and balance, even in the initial stages of the disease.

Physical therapy and exercise have been shown to effectively improve both motor and nonmotor symptoms of PD, suggesting that initiating these interventions earlier could help reduce disability and enhance long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence for Early and Regular Physical Therapy and Exercise in Parkinson's Disease. Ellis, TD., Colón-Semenza, C., DeAngelis, TR., et al.[2022]

Longitudinal analysis of data from 4674 individuals with Parkinson's disease showed that greater duration and intensity of exercise are linked to a lower risk of hospitalization.

In contrast, increased use of physical therapy (PT) and occupational therapy was associated with a higher likelihood of hospital encounters, suggesting that while PT may help identify at-risk patients, it does not prevent hospitalizations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Exercise and Rehabilitation Therapy on Risk of Hospitalization in Parkinson's Disease. Kannarkat, GT., Rafferty, MR., Luo, S., et al.[2023]

The proactive physical therapy (PAPT) program for people with Parkinson disease (PD) was successfully implemented at a rehabilitation center, targeting individuals before significant mobility issues arose, and resulted in a doubling of participants engaging in regular exercise over six months.

Participants in the PAPT program reported substantial physical and emotional benefits, with a notable increase in aerobic exercise participation and balance activities, highlighting the program's effectiveness in promoting long-term independent exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using Implementation Frameworks to Provide Proactive Physical Therapy for People With Parkinson Disease: Case Report. Rafferty, MR., MacDonald, J., Byskosh, A., et al.[2020]

Physical therapy (PT) significantly improves activities of daily living (ADLs) and stride length in patients with Parkinson's disease, with effect sizes of 0.40 and 0.46 respectively, based on a meta-analysis of studies published up to 1999.

While PT shows promise in enhancing walking speed (effect size of 0.49), the results are more variable, and neurologic signs did not show significant improvement, indicating that while PT is beneficial, its effects can vary among different aspects of Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of physical therapy in Parkinson's disease: a research synthesis. de Goede, CJ., Keus, SH., Kwakkel, G., et al.[2019]

Exercise and rehabilitation programs become essential for Parkinson's disease patients when motor decline occurs despite DOPAtherapy, as they can help reduce daily life disability rather than directly improving core symptoms like bradykinesia or tremor.

Only a few well-designed studies exist on the effectiveness of rehabilitation in Parkinson's disease, but they suggest that early intervention with physiotherapy focusing on postural control and fall prevention can significantly benefit patients' independence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Exercices program and rehabilitation of motor disorders in Parkinson's disease]. Pélissier, J., Pérennou, D.[2006]

A four-month physical therapy program combined with drug therapy significantly improved clinical ratings and motor performance in Parkinson's patients compared to those receiving drug therapy alone.

Improvements were observed across various severity levels of symptoms and disease durations, suggesting that physical therapy is beneficial for a wide range of patients with Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rehabilitation and Parkinson's disease. Formisano, R., Pratesi, L., Modarelli, FT., et al.[2008]

Early and continuous rehabilitation, combined with appropriate medication, is crucial for improving the quality of life in patients with Parkinson's disease, as it promotes self-awareness and the importance of daily physical activity.

Rehabilitation is cost-effective, has no adverse effects, and can be performed at home, making it a vital component in preventing disability and enhancing patients' overall health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rehabilitation of patients with Parkinson disease]. Kwolek, A.[2015]

A large study involving 762 patients with mild to moderate Parkinson's disease found that individualized physiotherapy and occupational therapy did not lead to significant improvements in activities of daily living or quality of life compared to no therapy.

While there were slight improvements in health-related quality of life measures, these were not clinically meaningful, suggesting that current low-dose, patient-centered therapy approaches may not be effective for early-stage Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effectiveness and cost-effectiveness of physiotherapy and occupational therapy versus no therapy in mild to moderate Parkinson's disease: a large pragmatic randomised controlled trial (PD REHAB). Clarke, CE., Patel, S., Ives, N., et al.[2022]

A 20-week physical therapy program significantly improved disability and motor skills in 20 patients with Parkinson's disease, as measured by various scales including UPDRS and the Ten-Meter Walk test.

Improvements in motor function and quality of life were largely maintained even 3 months after the completion of the rehabilitation program, indicating the long-term benefits of sustained physical therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical therapy in Parkinson's disease: an open long-term rehabilitation trial. Pellecchia, MT., Grasso, A., Biancardi, LG., et al.[2022]

Current medical treatments for Parkinson's disease are only partially effective, highlighting the need for additional support through physical and occupational therapy.

This review emphasizes the importance of a multidisciplinary approach, detailing how physical and occupational therapists can uniquely and collaboratively help patients manage daily activities and overcome challenges related to their condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical therapy and occupational therapy in Parkinson's disease. Radder, DLM., Sturkenboom, IH., van Nimwegen, M., et al.[2018]

Citations

1. academic.oup.com academic.oup.com/ptj/article/102/4/pzab302/6485202

Physical Therapist Management of Parkinson Disease Two high-quality19,25 and 2 moderate-quality studies29,32 revealed improvements in gait-related outcomes, including the 6-Minute Walk Test (6MWT) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8609713/

Effectiveness of Long-Term Physiotherapy in Parkinson's ... This review provided evidence that long-term physiotherapy has beneficial impact on motor symptoms and antiparkinsonian medication dose in PD patients.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32917125/

Physiotherapy in Parkinson's Disease: A Meta-Analysis of ... Conventional physiotherapy significantly improved motor symptoms, gait, and quality of life. Resistance training improved gait. Treadmill training improved gait ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2807484

Type, Timing, Frequency, and Durability of Outcome ... This systematic review and meta-analysis evaluates the type, timing, frequency, and duration of physical therapy for Parkinson disease and ...

5. jneuroengrehab.biomedcentral.com jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-025-01616-w

Is physical therapy recommended for people with parkinson's ... Despite the low-to-moderate quality of data, the few available rehabilitation studies suggested that PT could improve dynamic and static balance ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9046970/

Physical Therapist Management of Parkinson Disease Physical therapists should implement resistance training to reduce motor disease severity and improve strength, power, nonmotor symptoms, functional outcomes, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36602886/

Physical exercise for people with Parkinson's disease The evidence is very uncertain about the effect of physical exercise on the risk of adverse events (very low confidence). Across outcomes, we ...

8. jnnp.bmj.com jnnp.bmj.com/content/95/11/1077

Exercise as medicine in Parkinson's disease Exercise is safe and represents a cornerstone in PD rehabilitation, but exercise may have even more fundamental benefits that could change clinical practice.

9. apdaparkinson.org apdaparkinson.org/article/physical-therapy-and-parkinsons-disease-faqs/

Physical Therapy for Parkinson's Disease | APDA Physical therapy and exercise are crucial aspects of Parkinson's disease (PD) treatment and APDA has many ways to help you get up and moving.