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

Trial Summary

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 data supports the effectiveness of this treatment for Parkinson's Disease with Orthostatic Hypotension?

Research suggests that managing blood pressure abnormalities, like orthostatic hypotension, in Parkinson's Disease can help prevent cognitive decline by maintaining stable blood flow to the brain, which is crucial for cognitive health. ^{1 2 3 4 5}

Is tilt table therapy with fludrocortisone safe for Parkinson's patients with orthostatic hypotension?

Fludrocortisone has been shown to be safe in treating orthostatic hypotension in Parkinson's patients, with studies reporting no adverse reactions. It helps manage blood pressure effectively, making it a safe option for this condition. ^{1 6 7 8 9}

How does tilt table therapy differ from other treatments for Parkinson's disease with orthostatic hypotension?

Tilt table therapy is unique because it involves physically tilting the patient to improve blood flow and reduce symptoms of orthostatic hypotension (a drop in blood pressure when standing up), rather than using medication. This approach focuses on managing blood pressure changes through positioning, which can help improve symptoms without the side effects of drugs. ^{1 2 3 10 11}

What is the purpose of this trial?

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Besides causing symptoms that impair movement, PD also causes non-motor symptoms, such as problems thinking and orthostatic hypotension (OH), i.e., low blood pressure (BP) when standing. About one-third of people with PD have OH, which can cause sudden, temporary symptoms while upright, including lightheadedness, dizziness, and fainting. People with PD and OH can also experience problems thinking that happen only while upright and not while sitting - this can occur without other symptoms, such as feeling dizzy or faint. However, the level of low BP that can affect thinking remains unknown, and no guidelines exist for treating OH when it happens without symptoms. This is significant because OH could be a treatable risk factor for thinking problems in PD, but OH is often not treated if people do not report obvious symptoms. This project's goal is to determine how BP affects brain function in PD. The proposed experiments will measure BP and brain blood flow continuously in real-time using innovative wearable technology. Persons with PD with OH and without OH will undergo repeated cognitive tests while supine (lying down) and while upright. I will study the associations between BP, thinking abilities, and brain blood flow, and will compare groups with and without OH. These findings could be important because if a certain level of BP correlates with thinking abilities, then treating OH in PD may prevent thinking problems, which would improve health-related quality of life and reduce disability and healthcare costs.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Transcranial Doppler ultrasonographic evaluation of cerebral circulation during passive tilting in patients with Parkinson's disease. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Caudate-anchored cognitive connectivity pursuant to orthostatic hypotension in early Parkinson's disease. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of orthostatic hypotension on cognition in Parkinson disease. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Cerebral autoregulation and white matter lesions in Parkinson's disease and multiple system atrophy. [2015]

5. Poland pubmed.ncbi.nlm.nih.gov

Cardiovascular dysautonomia and cognition in Parkinson's Disease - a possible relationship. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson's disease. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Pharmacology of orthostatic hypotension in Parkinson's disease: from pathophysiology to management. [2005]

9. Germany pubmed.ncbi.nlm.nih.gov

Ambulatory 24-hour blood pressure recordings in patients with Parkinson's disease with or without fludrocortisone. [2014]

10. United States pubmed.ncbi.nlm.nih.gov

Orthostatic hypotension and cognitive impairment in Parkinson's disease: Causation or association? [2018]

11. Germany pubmed.ncbi.nlm.nih.gov

Cognitive and MRI correlates of orthostatic hypotension in Parkinson's disease. [2021]