Tilt Table Therapy for Parkinson's Disease with Orthostatic Hypotension

Overseen By Michael Skipworth, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Must not be taking: Antihypertensives, Diuretics, Prostate medications

Disqualifiers: Dementia, Diabetes, Heart failure, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how blood pressure affects thinking and brain blood flow in people with Parkinson's disease who also experience orthostatic hypotension (a drop in blood pressure when standing). Participants will undergo cognitive tests while lying down and standing up, allowing researchers to determine if changes in blood pressure impact mental abilities. The goal is to find ways to prevent thinking problems by treating blood pressure issues. Individuals with Parkinson's disease who do not have severe involuntary movements, have not undergone deep brain stimulation surgery, and are not on certain blood pressure medications might be suitable for this trial.

As an unphased study, this trial offers participants the chance to contribute to groundbreaking research that could lead to better management of Parkinson's disease symptoms.

Do I need to stop taking my current medications for the trial?

If you are taking medications for high blood pressure, diuretics (water pills), or medications for an enlarged prostate, you may need to stop them 48 hours before the study visit. Please discuss this with your doctor to see if it's safe for you to discontinue these medications.

What prior data suggests that tilt table therapy is safe for Parkinson's disease with orthostatic hypotension?

Research has shown that fludrocortisone, a treatment sometimes used for low blood pressure when standing, is generally well-tolerated. One study found that 61% of people taking fludrocortisone reported at least one side effect, compared to 71% of those taking a placebo. This suggests that fludrocortisone might have fewer side effects than expected.

Although the evidence remains limited, fludrocortisone is considered safe for treating severe low blood pressure, especially when other treatments fail. For people with Parkinson's disease, the effects of fludrocortisone on blood pressure remain unclear, but it has been used in similar conditions before. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how tilt table therapy might help people with Parkinson's disease who also experience orthostatic hypotension, a drop in blood pressure when standing up. Unlike standard medications that mainly focus on controlling symptoms of orthostatic hypotension, this approach investigates how changing body position affects cognitive function and brain blood flow. By alternating cognitive testing between supine (lying down) and upright positions, researchers aim to understand the connection between blood pressure changes and cognitive performance. This could lead to new insights into managing both motor and non-motor symptoms of Parkinson's disease more effectively.

What evidence suggests that tilt table therapy could be effective for Parkinson's disease with orthostatic hypotension?

Research has shown that treating orthostatic hypotension (OH) in people with Parkinson's disease (PD) might help with cognitive issues. Fludrocortisone, a medication for OH, has shown promising results. Studies have demonstrated that it reduces the blood pressure drop when standing, a primary symptom of OH. Specifically, for people with PD, fludrocortisone significantly improved blood pressure control, reducing the drop by 37% during standing tests. This trial will explore how blood pressure management affects cognition and brain blood flow in PD, with participants undergoing cognitive testing in both supine and upright positions. Managing OH with fludrocortisone may help prevent cognitive issues related to low blood pressure in PD. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for people over 50 with Parkinson's Disease (PD) who can walk without help and speak English fluently. They should be in the early to moderate stages of PD but not have unstable medical conditions, uncontrolled diabetes, recent fainting episodes, severe involuntary movements, significant carotid artery narrowing, hearing or vision impairments not corrected by devices, pregnancy, dementia including PD dementia, a history of stroke or brain surgery.

Inclusion Criteria

I have been diagnosed with Parkinson's Disease.

I am at least 50 years old.

Proficiency in the English language (native English speaker level)

Exclusion Criteria

I have been diagnosed with dementia.

I am taking medication for high blood pressure or medications that affect my blood pressure.

I don't have large involuntary movements or they're controlled by medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 hours

1 visit (in-person)

Baseline Study Visit

Participants undergo baseline assessments including continuous BP monitoring and cognitive testing in supine and upright positions

3 hours

1 visit (in-person)

Cognitive Testing

Participants perform cognitive tasks while supine and upright, with continuous monitoring of BP and cerebral oxygenation

1 hour 20 minutes

Follow-up

Participants are monitored for safety and effectiveness after cognitive testing

up to 30 months

What Are the Treatments Tested in This Trial?

Interventions

• Blood Pressure Effects on Cognition and Brain Blood Flow in PD

Trial Overview The study tests how blood pressure affects thinking and brain blood flow in PD patients when they change positions from lying down to standing up. It uses wearable technology to monitor these changes continuously during cognitive tests performed both while supine and upright.

How Is the Trial Designed?

Group I: Upright cognitive testing first Experimental Treatment 1 Intervention

The cognitive testing sessions will be alternated between supine and upright positions. This group will perform cognitive testing sessions in the following order: 1) upright, 2) supine, 3) upright, 4) supine.

Group II: Supine cognitive testing first Experimental Treatment 1 Intervention

The cognitive testing sessions will be alternated between supine and upright positions. This group will perform cognitive testing sessions in the following order: 1) supine, 2) upright, 3) supine, 4) upright.

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Beth Israel Deaconess Medical Center

Collaborator

Trials

872

Recruited

12,930,000+

Drexel University

Collaborator

Trials

160

Recruited

48,600+

Published Research Related to This Trial

In a study involving 17 patients with idiopathic Parkinson's disease, nonpharmacological therapy did not significantly improve symptoms of orthostatic hypotension, indicating limited efficacy of this approach.

Both fludrocortisone and domperidone were effective in improving clinical global impression and orthostatic symptoms, with domperidone showing a greater trend in reducing blood pressure drops during tilt table testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson's disease. Schoffer, KL., Henderson, RD., O'Maley, K., et al.[2019]

Dementia in advanced Parkinson's Disease is linked to cognitive impairment and cardiovascular issues, particularly blood pressure abnormalities like orthostatic hypotension, which can worsen cognitive decline.

24-hour ambulatory blood pressure monitoring is recommended for patients with Parkinson's Disease showing symptoms of dysautonomia, as these blood pressure issues can often go unnoticed and significantly impact cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular dysautonomia and cognition in Parkinson's Disease - a possible relationship. Kwaśniak-Butowska, M., Dulski, J., Pierzchlińska, A., et al.[2021]

Orthostatic hypotension and cognitive impairment in Parkinson's disease (PD) are interrelated, potentially due to recurrent low blood pressure leading to reduced blood flow to the brain, which may cause cognitive decline.

Evidence suggests that noradrenergic denervation, which affects blood pressure regulation, may also contribute to cognitive impairment in PD, indicating that addressing blood pressure issues could improve cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orthostatic hypotension and cognitive impairment in Parkinson's disease: Causation or association? McDonald, C., Newton, JL., Burn, DJ.[2018]

In a study involving six parkinsonian patients suffering from severe postural hypotension due to levodopa therapy, treatment with fludrocortisone acetate (0.05 to 0.2 mg daily) for six to ten months successfully normalized blood pressure and alleviated symptoms of light-headedness and syncope.

The treatment was found to be both effective and safe, with no reported adverse reactions, making fludrocortisone acetate a promising option for managing postural hypotension in patients on levodopa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levodopa-induced postural hypotension. Treatment with fludrocortisone. Hoehn, MM.[2019]

Orthostatic hypotension is common in the elderly and affects up to 20% of patients with Parkinson's disease, indicating a significant health concern in this population.

While midodrine and fludrocortisone are recommended as first-choice treatments for managing orthostatic hypotension in Parkinson's disease, there is currently no specific clinical trial data on their efficacy or effects on related morbidity, highlighting the need for further research and the potential importance of nonpharmacological management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of orthostatic hypotension in Parkinson's disease: from pathophysiology to management. Pathak, A., Senard, JM.[2005]

In a study of 104 early Parkinson's disease patients, those with orthostatic hypotension showed altered cognitive connectivity patterns, indicating that hemodynamic stress can influence how different brain regions communicate during cognitive tasks.

Despite the presence of orthostatic hypotension and amyloid-β accumulation in some patients, overall cognitive performance did not differ, suggesting that the brain can adapt its neural connections in response to stressors like orthostatic hypotension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caudate-anchored cognitive connectivity pursuant to orthostatic hypotension in early Parkinson's disease. Yoo, SW., Ha, S., Oh, YS., et al.[2023]

In a study involving 55 participants with Parkinson's disease (PD), those with orthostatic hypotension (PDOH) exhibited more severe cognitive impairments when standing compared to those without OH, indicating that posture can significantly affect cognitive function in PD.

The findings suggest that orthostatic hypotension may lead to acute and reversible cognitive deficits, highlighting the importance of assessing cognitive function in different postures to better understand and potentially intervene in cognitive disturbances associated with PD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of orthostatic hypotension on cognition in Parkinson disease. Centi, J., Freeman, R., Gibbons, CH., et al.[2022]

Parkinson's disease patients without orthostatic hypotension showed no significant difference in daytime and nighttime systolic blood pressure, indicating a lack of normal blood pressure variation, while those on fludrocortisone therapy exhibited higher nighttime blood pressure compared to daytime levels.

Fludrocortisone treatment effectively elevated the daytime blood pressure of Parkinson's disease patients to levels comparable to healthy controls, suggesting its efficacy in managing orthostatic hypotension in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ambulatory 24-hour blood pressure recordings in patients with Parkinson's disease with or without fludrocortisone. Hakamäki, T., Rajala, T., Lehtonen, A.[2014]

Cerebral autoregulation in Parkinson's disease (PD) and multiple system atrophy (MSA) adapts to maintain blood supply across a wider range of blood pressure values, which may help patients tolerate low blood pressure when standing (orthostatic hypotension).

This adaptation could increase the risk of high blood pressure episodes (supine hypertension), potentially leading to silent brain damage, suggesting that monitoring cerebral autoregulation could help manage both orthostatic symptoms and prevent cognitive decline in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral autoregulation and white matter lesions in Parkinson's disease and multiple system atrophy. Indelicato, E., Fanciulli, A., Poewe, W., et al.[2015]

In a study of 30 patients with Parkinson's disease and 15 healthy controls, it was found that patients had lower cerebral blood flow velocity (CBFV) at rest and exhibited delayed cardiovascular responses during a tilt test, indicating potential subclinical autonomic dysfunction.

While blood pressure responses differed between groups during tilting—patients experienced a decrease in systolic blood pressure while controls showed an increase—both groups had similar drops in CBFV, highlighting the impact of Parkinson's disease on cardiovascular regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Doppler ultrasonographic evaluation of cerebral circulation during passive tilting in patients with Parkinson's disease. Mihci, E., Dora, B., Balkan, S.[2016]

In a study of 48 Parkinson's disease patients, those with orthostatic hypotension (OH) exhibited significantly worse cognitive performance in areas like attention and memory compared to those without OH.

Despite the cognitive deficits observed in patients with OH, the study found no differences in brain vascular lesions between the two groups, suggesting that cerebrovascular disease may not be the underlying cause of cognitive impairment in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive and MRI correlates of orthostatic hypotension in Parkinson's disease. Pilleri, M., Facchini, S., Gasparoli, E., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8128337/

Fludrocortisone for orthostatic hypotension - PMC The randomized studies found that fludrocortisone reduced blood pressure drop compared to placebo (an inactive medication) in people with severe diabetic ...

2. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012868.pub2/full

Fludrocortisone for orthostatic hypotension - Veazie, S - 2021 The randomized studies found that fludrocortisone reduced blood pressure drop compared to placebo (an inactive medication) in people with severe ...

3. nice.org.uk nice.org.uk/advice/esuom20

Postural hypotension in adults: fludrocortisone | Advice This study found a statistically significant improvement in the orthostatic domain score of the Composite Autonomic Symptom Scale (COMPASS\u2011 ...

4. cureus.com cureus.com/articles/398619-pharmacological-interventions-for-orthostatic-hypotension-a-systematic-review

Pharmacological Interventions for Orthostatic Hypotension [33] assessed 13 participants with PD and found a 37% reduction in DBP drop during orthostatic challenges, alongside an 11% increase in ...

5. practicalneurology.com practicalneurology.com/diseases-diagnoses/movement-disorders/diagnosis-and-management-of-orthostatic-hypotension-in-individuals-with-parkinson-disease/37651/

Orthostatic Hypotension in People with Parkinson Disease During a 2-week study, participants with PD treated with fludrocortisone demonstrated significant improvement in orthostatic vital signs; ...

6. nice.org.uk nice.org.uk/advice/esuom20/chapter/evidence-review-safety

Postural hypotension in adults: fludrocortisone At least 1 adverse effect was reported during treatment by 61% of people receiving fludrocortisone compared with 71% receiving placebo; data for ...

7. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/573468

Levodopa-Induced Postural Hypotension Fludrocortisone acetate is an effective and safe drug for the treatment of severe and otherwise intractable postural hypotension secondary to therapy with ...

8. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012868.pub2/full?UNLID=48839112120257114352

Fludrocortisone for orthostatic hypotension - Veazie, S - 2021 For people with Parkinson disease, we found very‐low certainty evidence about the effects of fludrocortisone on drop in BP compared to ...

9. ajconline.org ajconline.org/article/S0002-9149(20)30102-8/fulltext

Cardiovascular Safety Considerations in the Treatment ... Neurogenic orthostatic hypotension (nOH), a drop in blood pressure upon standing resulting from autonomic malfunction, may cause debilitating symptoms.