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A Study to Systematically Assess the Efficacy and Safety of Intravenous Albumin Infusions in Severe POTS

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ClinicalTrials.gov Identifier: NCT03365414
Recruitment Status : Not yet recruiting
First Posted : December 7, 2017
Last Update Posted : August 28, 2018
Sponsor:
Information provided by (Responsible Party):
Zaeem Siddiqi, University of Alberta

Brief Summary:

POTS is a relatively common condition that affects millions of patients around the globe. It has an estimated prevalence of 170/100,000 with approximately 80% of patients being women of childbearing age. POTS is characterized by an excessive heart rate increase on assuming an upright posture, either standing or even sitting and leading to disabling palpitations, light-headedness, and even in syncope in severe cases. More than 95% patients with POTS have pronounced cardiovascular deconditioning and show marked exercise intolerance. The severity of POTS is variable. In mild cases the affected patient may continue with routine activities with minimal limitations. Severe form of the disease precludes most normal life activities, such as sitting upright, walking or standing to perform even basic house chores. An estimated 40% of patients with POTS have a resistant form of the condition that is nonresponsive or mildly responsive to all treatments resulting in continued functional limitations in the long term.

Many of the currently available treatments in POTS are geared towards increasing blood pressure. These include compression stockings, increased daily fluid intake and increased salt ingestion. Saline infusions may be helpful in certain patients in the short term, though many do not respond. The effectiveness of medications varies greatly, with many patient failing to improve.

A small series of clinical patients suffering from severe POTS have shown robust response to weekly albumin therapy, which supports the hypothesis that periodic albumin infusions will provide significant and sustained symptomatic relief to patients with severe POTS.

This pilot study will explore the effectiveness of albumin infusions as a treatment for POTS. Eligible patients will receive weekly intravenous infusions of 5% Albumin or Saline in a double blinded fashion for 4 weeks and will crossover to the other infusion for 4 weeks after an intervening 4-week washout period. The participants will be required to maintain a daily diary of their symptoms during the screening, the study and washout periods. Any possible adverse effects as the result of infusions will be documented. Outcome measures will be quantified and validated at the end of each study period and the percentage reduction of tachycardia will be determined at the completion of each study arm.


Condition or disease Intervention/treatment Phase
Postural Orthostatic Tachycardia Syndrome Biological: Albumin (Human) 5%, USP Drug: Normal Saline 0.9% Infusion Solution Bag Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Phase I (albumin or normal saline): 4 weeks -> washout/crossover: 4 weeks ->Phase II(albumin or normal saline, whichever wasn't administered in phase I): 4 weeks
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Double Blind Randomized Controlled Crossover Study to Systematically Assess the Efficacy and Safety of Intravenous Albumin Infusions in Severe Postural Orthostatic Tachycardia Syndrome
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : March 2021

Arm Intervention/treatment
Phase I
Placebo ( Normal Saline 0.9% Infusion Solution Bag) or active comparator (Albumin (Human) 5%, USP)
Biological: Albumin (Human) 5%, USP
Albumin (Human) 5%, USP. Intravenous Solution. Plasma Substitute/Blood Derivative

Drug: Normal Saline 0.9% Infusion Solution Bag
Placebo Normal Saline 0.9% Infusion Solution Bag.
Other Name: sodium chloride 0.9% infusion solution bag

Phase II
Placebo ( Normal Saline 0.9% Infusion Solution Bag) or active comparator (Albumin (Human) 5%, USP), whichever was not not administered in Phase I
Biological: Albumin (Human) 5%, USP
Albumin (Human) 5%, USP. Intravenous Solution. Plasma Substitute/Blood Derivative

Drug: Normal Saline 0.9% Infusion Solution Bag
Placebo Normal Saline 0.9% Infusion Solution Bag.
Other Name: sodium chloride 0.9% infusion solution bag




Primary Outcome Measures :
  1. Severity of Orthostatic Intolerance [ Time Frame: Change in Orthostatic Symptom Grading Scale (OSGS) scores from baseline to end of first arm (1-4 weeks), from end of washout (5-8 weeks) to end of second arm (9-12 weeks) and at end of study (16 week duration). ]
    Self-reported severity of orthostatic intolerance assessed by the Orthostatic Symptom Grading Scale (OSGS) scores. Recorded daily. Each item is scored 0-4 (0= lowest severity; 4=greatest severity), yielding a total between 0 and 25.


Secondary Outcome Measures :
  1. Disability Assessment [ Time Frame: Weekly through study completion, 16 week duration ]
    The Health Assessment Questionnaire (HAQ) score consists of questions referring to 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific subcategory items. The standard disability score is calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered, yielding a score from 0 (without any difficulty) to 3 (unable to do).

  2. Degree of cardiovascular improvement - Heart rate [ Time Frame: Changes in heart rate (BPM) from baseline to end of first arm (1-4 weeks), from end of washout (5-8 weeks) to end of second arm (9-12 weeks) and at end of study (16 week duration). ]
    Degree of improvement from baseline in the severity of tachycardia (beats per minute) on a 10-minute head up tilt table test (HUTT). The tilt table test will be performed at baseline and at the end-points of each arm of the study to measure degree of heart rate increment and pulse pressure reduction within 10 minutes of assuming an upright posture.

  3. Degree of cardiovascular improvement - Pulse [ Time Frame: Changes in blood pressure (mm Hg) from baseline to end of first arm (1-4 weeks), from end of washout (5-8 weeks) to end of second arm (9-12 weeks) and at end of study (16 week duration). ]
    Degree of improvement from baseline in the pulse pressure (mm Hg) on a 10-minute head up tilt table test (HUTT). The tilt table test will be performed at baseline and at the end-points of each arm of the study to measure degree of heart rate increment and pulse pressure reduction within 10 minutes of assuming an upright posture.

  4. Change in maximal exercise capacity - Cardiopulmonary exercise testing [ Time Frame: Changes in aerobic capacity between baseline and end of first arm (1-4 weeks), and end of washout (5-8 weeks) to end of second arm (9-12 weeks). Follow-up data at end of study (16 week duration). ]

    Cardiopulmonary exercise testing (CPX) using breath by breath gas-analysis measures variables related to cardiorespiratory function, including expiratory ventilation and pulmonary gas exchange (oxygen uptake (VO2) and carbon dioxide (VCO2).The standard expression of aerobic working capacity is the maximum VO2.

    VO2 max reached during a symptom-limited incremental CPX protocol is commonly expressed as O2 per kg-1 per min -1.


  5. Change in maximal exercise capacity - Electrocardiogram [ Time Frame: Changes in aerobic capacity between baseline and end of first arm (1-4 weeks), and end of washout (5-8 weeks) to end of second arm (9-12 weeks). Follow-up data at end of study (16 week duration). ]
    Electrocardiogram (ECG) measures allows for quantitatively linking metabolic, cardiovascular and pulmonary responses to exercise.

  6. Change in maximal exercise capacity - Heart rate [ Time Frame: Changes in aerobic capacity between baseline and end of first arm (1-4 weeks), and end of washout (5-8 weeks) to end of second arm (9-12 weeks). Follow-up data at end of study (16 week duration). ]
    Pulse measures allows for quantitatively linking metabolic, cardiovascular and pulmonary responses to exercise.

  7. Change in maximal exercise capacity - Blood Pressure [ Time Frame: Changes in aerobic capacity between baseline and end of first arm (1-4 weeks), and end of washout (5-8 weeks) to end of second arm (9-12 weeks). Follow-up data at end of study (16 week duration). ]
    Blood pressure measures allows for quantitatively linking metabolic, cardiovascular and pulmonary responses to exercise.



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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females, ages between 18 to 69 years
  2. Disease duration of >12 months
  3. Diagnosis of idiopathic POTS confirmed by absolute heart rate increase to >120 beats/minute or increase by >30 beats/minute from baseline within 10 minutes on HUTT without orthostatic hypotension (i.e. drop in systolic BP >30mm of Hg) Plus, • Tachycardia, associated with symptoms of orthostatic intolerance (light-headedness, palpitations, chest pain, nausea, visual blurring, sweating, limb paresthesias)

1. Abnormal sweat testing in the leg/foot (to confirm neuropathic POTS) 2. Severe disease manifestations defined as meeting all three of the following criteria:

  1. Severe orthostatic intolerance - Orthostatic Symptoms Grading Scale (OSGS) Score >12
  2. Severe symptoms that preclude activities of daily living i.e. Patient-Reported Outcomes Measurement Information System, Health Assessment Questionnaire (PHAQ 20) score >36
  3. Lack or limited response to an adequate trial (8 weeks' duration) of at least two of the following standard treatment modalities for POTS including

i. Increased daily intake of salt & water ii. Midodrine iii. Fludrocortisone iv. Beta blockers v. Selective Serotonin Reuptake Inhibitors vi. Desmopressin

Exclusion Criteria:

  1. Orthostatic hypotension - a decline of 30mm Hg or more in systolic blood pressure or 20mm Hg or more in mean blood pressure within 3 minutes of standing or head-up tilt.
  2. Abnormal ECG or echocardiogram.
  3. Recent history (<1 month) of protracted diarrhea or vomiting or hospitalization.
  4. History of significant psychiatric or eating disorders.
  5. Pregnancy or lactation.
  6. History of allergic reactions to human albumin.
  7. Patients on diuretic, laxative or antihypertensive medications (except beta blockers)
  8. Systemic illness affecting autonomic function (pheochromocytoma, congestive heart failure, hypertension, renal or hepatic disease, severe anemia, alcoholism, malignant neoplasm, diabetes, hypothyroidism, or stroke).
  9. Presence of any secondary cause of POTS - amyloidosis, sarcoidosis, alcoholism, lupus, Sjögren's syndrome, chemotherapy, and heavy metal poisoning.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03365414


Contacts
Contact: Derrick Blackmore, BSc 780-407-3367 dblackmo@ualberta.ca

Sponsors and Collaborators
University of Alberta
Investigators
Principal Investigator: Zaeem Siddiqi, MD PhD University of Alberta

Responsible Party: Zaeem Siddiqi, Professor, University of Alberta, University of Alberta
ClinicalTrials.gov Identifier: NCT03365414     History of Changes
Other Study ID Numbers: ZS-POTS-2017
First Posted: December 7, 2017    Key Record Dates
Last Update Posted: August 28, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share individual participant data (IPD) available with other researchers.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Zaeem Siddiqi, University of Alberta:
Postural Orthostatic Tachycardia Syndrome
POTS
Syncope
Vasovagal
Hypotension
Tachycardia

Additional relevant MeSH terms:
Syndrome
Tachycardia
Postural Orthostatic Tachycardia Syndrome
Disease
Pathologic Processes
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Pharmaceutical Solutions