Clinical trial NCT04920552: Abdominal Binders to Treat Orthostatic Hypotension in Parkinsonian Syndromes
Official title: Abdominal Binders to Treat Orthostatic Hypotension in Parkinsonian Syndromes: a Randomized, Placebo-controlled, Double-blind, Crossover Phase II Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Parkinson Disease
Multiple System Atrophy, Parkinson Variant
Orthostatic; Hypotension, Neurogenic
Lead sponsor: Universitätsklinik für Neurologie, Innsbruck
Sponsor class: OTHER
First posted: 2021-06-10
Enrollment: 30
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: monocentric, randomized, placebo-controlled, double-blind, crossover phase II trial with an open-label treatment extension phase
Primary purpose: TREATMENT

Brief summary: The purpose of the present clinical trial is to determine whether the use of an elastic abdominal binder is effective in the non-pharmacological management of symptomatic, neurogenic orthostatic hypotension (OH) in individuals suffering from Parkinson's disease (PD) or Parkinson variant multiple system atrophy (MSA-P).

Detailed description: This is a monocentric, randomized, placebo-controlled, double-blind, crossover phase II clinical trial with an open-label treatment extension phase. The investigators plan to recruit n = 30 individuals with MSA-P or PD with known or suspected OH.

At the Screening Visit, after patient information and written informed consent, the participants will first undergo a comprehensive neurological and cardiological evaluation, as well cardiovascular autonomic function testing to confirm the diagnosis of symptomatic, neurogenic OH.

Afterwards, the participants will be asked to wear physical activity monitoring (PAM) sensors for five consecutive days and to measure the blood pressure (BP) regularly following a home BP diary (i.e. Home Phase I).

On treatment day-1 (i.e. Visit 1), the participants will undergo an instrumented in-lab gait analysis, followed by a head-up tilt and active standing test. Afterwards, they will wear the first type of binder for two hours (either the investigational elastic abdominal binder or the placebo-comparator binder, depending on the randomization assignment). At the end of the two hours, the participants will repeat the in-lab gait analysis and the head-up tilt-/active standing test.

After one-day wash-out, the same procedure of treatment day-1 (i.e. Visit 1) will be repeated with the outstanding type of binder (i.e. treatment day-2, Visit 2).

At the end of this, all participants will be invited to wear the investigational elastic abdominal binder and the PAM sensors for five more days and to repeat the home BP measurements (i.e. Home Phase II).

A final follow-up visit is scheduled to return the PAM sensors, the BP monitor and to detect eventual adverse and serious adverse events occurred during Home Phase II.

Eligibility criteria: Inclusion Criteria:

* diagnosis of possible or probable MSA-P (Gilman 2008) or clinically established PD (Postuma 2015);
* 50 to 85 years of age;
* laboratory-confirmed symptomatic (i.e. OHQ - OH Symptom Assessment item #1 ≥ 4), neurogenic OH at screening visit or previously diagnosed as such (i.e. neurogenic OH ratio \[≤ 0.492 Δ heart rate rise/systolic BP fall\] or missing BP overshoot at phase IV of Valsalva maneuver;
* stable medication schedule in the preceding 3 weeks;
* no infectious disease in the preceding 3 weeks;
* Hoehn \& Yahr stage ≤ 3;
* gait item of the Unified MSA Rating Scale (UMSARS) Part II or the Movement Disorder Society - Unified PD Rating Scale (MDS-UPDRS) Part III score \< 3;
* body sway item of the UMSARS II/MDS-UPDRS III score \< 3;
* arising from chair item of the UMSARS II/MDS-UPDRS III score \< 3;
* full legal capacity;
* written informed consent has been obtained.

Exclusion Criteria:

* participation in other interventional trials;
* prescribed and regular use of abdominal binders OR compression stockings for OH treatment;
* other major neurologic or psychiatric diseases which could influence OH or gait;
* untreated diabetes mellitus with clinical features of peripheral neuropathy;
* non-neurological causes of gait disorders;
* major cardiac diseases (ischemic, structural, arrhythmias);
* evidence of varices (venous insufficiency stage ≥ C2, "varicose veins");
* known abdominal aortic aneurism;
* indwelling catheterisation;
* recent surgery (3 months) requiring anaesthesia;
* known or suspected pregnancy;
* breast-feeding female participants.

Primary outcomes:
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on mean BP change (mmHg) after 3rd minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
Secondary outcomes:
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on systolic BP change (mmHg) after 3rd minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on diastolic BP change (mmHg) after 3rd minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on mean BP change (mmHg) after 10th minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on systolic BP change (mmHg) after 10th minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on diastolic BP change (mmHg) after 10th minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on absolute mean orthostatic BP value (mmHg) after 3rd minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on absolute systolic orthostatic BP value (mmHg) after 3rd minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on absolute diastolic orthostatic BP value (mmHg) after 3rd minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on absolute mean orthostatic BP value (mmHg) after 10th minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on absolute systolic orthostatic BP value (mmHg) after 10th minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on absolute diastolic orthostatic BP value (mmHg) after 10th minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on OH symptom severity after 3rd minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on OH symptom severity after 10th minute of head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on mean BP change (mmHg) after 3rd minute of active standing test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on systolic BP change (mmHg) after 3rd minute of active standing test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on diastolic BP change (mmHg) after 3rd minute of active standing test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on absolute mean orthostatic BP value (mmHg) after 3rd minute of active standing test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on absolute systolic orthostatic BP value (mmHg) after 3rd minute of active standing test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on absolute diastolic orthostatic BP value (mmHg) after 3rd minute of active standing test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on OH symptom severity after 3rd minute of active standing test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on supine mean BP value (mmHg) at 10th minute before head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on supine systolic BP value (mmHg) at 10th minute before head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on supine diastolic BP value (mmHg) at 10th minute before head-up tilt test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on supine mean BP value (mmHg) at 5th minute before active standing test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on supine systolic BP value (mmHg) at 5th minute before active standing test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on supine diastolic BP value (mmHg) at 5th minute before active standing test with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on in-lab sensor-based mean gait velocity with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus a placebo binder for two hours on in-lab sensor-based mean stride length with respect to baseline.
timeFrame: 3 days
measure: Effect of wearing an elastic abdominal binder versus no binder for five consecutive days on lowest systolic BP values (mmHg) after 3rd minute of home active standing test in the early morning.
timeFrame: 10 days
measure: Effect of wearing an elastic abdominal binder versus no binder for five consecutive days on lowest systolic BP values (mmHg) after 3rd minute of home active standing test 60 minutes after lunch.
timeFrame: 10 days
measure: Effect of wearing an elastic abdominal binder versus no binder for five consecutive days on highest supine systolic BP values (mmHg) at 5th minute before home active standing test in the evening.
timeFrame: 10 days
measure: Effect of wearing an elastic abdominal binder versus no binder for five consecutive days on OH symptom severity.
timeFrame: 10 days
measure: Effect of wearing an elastic abdominal binder versus no binder for five consecutive days on overall mobility.
timeFrame: 10 days
measure: Effect of wearing an elastic abdominal binder versus no binder for five consecutive days on PAM-derived number of walking bouts.
timeFrame: 10 days
measure: Effect of wearing an elastic abdominal binder versus no binder for five consecutive days on PAM-derived duration of walking bouts.
timeFrame: 10 days
measure: Effect of wearing an elastic abdominal binder versus no binder for five consecutive days on PAM-derived mean gait velocity.
timeFrame: 10 days
measure: Effect of wearing an elastic abdominal binder versus no binder for five consecutive days on PAM-derived mean stride length.
timeFrame: 10 days
measure: Number of participants with treatment-related adverse events.
timeFrame: 8 days
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
state: Tyrol
Study officials:
References:
citation: Fanciulli A, Goebel G, Metzler B, Sprenger F, Poewe W, Wenning GK, Seppi K. Elastic Abdominal Binders Attenuate Orthostatic Hypotension in Parkinson's Disease. Mov Disord Clin Pract. 2015 Nov 27;3(2):156-160. doi: 10.1002/mdc3.12270. eCollection 2016 Mar-Apr.
citation: Fanciulli A, Wenning GK. Multiple-system atrophy. N Engl J Med. 2015 Jan 15;372(3):249-63. doi: 10.1056/NEJMra1311488. No abstract available.
citation: Fanciulli A, Leys F, Falup-Pecurariu C, Thijs R, Wenning GK. Management of Orthostatic Hypotension in Parkinson's Disease. J Parkinsons Dis. 2020;10(s1):S57-S64. doi: 10.3233/JPD-202036.