NCT02149901

Brief Summary

The specific aim of this study is to determine whether water ingestion potentiates the pressor response to pseudoephedrine in patients with primary disorders of autonomic failure. The study design will enable us to also evaluate the pressor response to water alone and to pseudoephedrine alone. In a secondary analysis, we will compare the results in patients with two autonomic disorders, pure autonomic failure (PAF) and multiple system atrophy (MSA). We hypothesize that drinking water following a dose of pseudoephedrine will lead to a greater increase in blood pressure than pseudoephedrine alone.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
35

participants targeted

Target at P50-P75 for early_phase_1

Timeline
Completed

Started Oct 2014

Longer than P75 for early_phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 26, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 29, 2014

Completed
4 months until next milestone

Study Start

First participant enrolled

October 1, 2014

Completed
6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2020

Completed
Last Updated

May 5, 2021

Status Verified

April 1, 2021

Enrollment Period

6.2 years

First QC Date

May 26, 2014

Last Update Submit

April 29, 2021

Conditions

Shy-Drager SyndromeMultiple System Atrophy

Keywords

Pure Autonomic FailureMultiple System AtrophyPseudoephedrineWaterOsmopressor

Outcome Measures

Primary Outcomes (1)

  • The primary outcome measure in each Aim will be the peak increase in systolic blood pressure after pseudoephedrine or placebo relative to baseline (delta SBP).

    between 60 and 120 minutes after pseudoephedrine or placebo

Secondary Outcomes (6)

  • Change in diastolic blood pressure relative to baseline

    between 60 and 120 minutes after pseudoephedrine or placebo

  • Change in heart rate relative to baseline

    between 60 and 120 minutes after pseudoephedrine or placebo

  • Absolute systolic blood pressure after treatment

    between 60 and 120 minutes after pseudoephedrine and placebo

  • Absolute diastolic blood pressure after treatment

    between 60 and 120 minutes after pseudoephedrine or placebo

  • area under the curve for systolic blood pressure from baseline to 135 minutes post-treatment

    from baseline to 135 minutes after pseudoephedrine or placebo

  • +1 more secondary outcomes

Study Arms (4)

Pseudoephedrine + 480 ml water

EXPERIMENTAL

Pseudoephedrine 30 mg PO 45 minutes before water 480 ml

Drug: Pseudoephedrine + 480 ml water

Pseudoephedrine + 50 ml water

PLACEBO COMPARATOR

Pseudoephedrine 30 mg PO 45 minutes before water 50 ml

Drug: Pseudoephedrine + 50 ml water

Placebo + 480 ml water (optional)

EXPERIMENTAL

Placebo PO 45 minutes before water 480 ml

Other: Placebo + 480 ml water (optional)

Placebo + 50 ml water (optional)

PLACEBO COMPARATOR

Placebo PO 45 minutes before water 50 ml

Other: Placebo + 50 ml water (optional)

Interventions

Pseudoephedrine + 480 ml waterDRUG

30 mg pseudoephedrine to be given with a pressor dose (480 ml) of drinking water

Also known as: Sudafed, drinking water
Pseudoephedrine + 480 ml water
Pseudoephedrine + 50 ml waterDRUG

Pseudoephedrine given with a non-pressor (50 ml) dose of drinking water

Also known as: Sudafed, drinking water
Pseudoephedrine + 50 ml water
Placebo + 480 ml water (optional)OTHER

placebo PO with a pressor (480 ml) dose of drinking water

Also known as: drinking water
Placebo + 480 ml water (optional)
Placebo + 50 ml water (optional)OTHER

placebo PO with a non-pressor (50 ml) dose of drinking water

Also known as: drinking water
Placebo + 50 ml water (optional)

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 18-80 years, with
  • Neurogenic orthostatic hypotension, ≥30 mmHg drop in SBP within 5 minutes of standing,
  • Associated with impaired autonomic reflexes, as determined by absence of blood pressure overshoot during phase IV of the valsalva maneuver,
  • Absence of other identifiable causes of autonomic neuropathy, and
  • Able and willing to provide informed consent

You may not qualify if:

  • Pregnancy
  • Current smoking habit
  • Systemic illnesses known to produce autonomic neuropathy, including but not limited to diabetes mellitus, amyloidosis, monoclonal gammopathy of unknown significance, and autoimmune neuropathies.
  • Known intolerance to pseudoephedrine
  • Pre-existing sustained severe hypertension (BP \> 180/110 mmHg in the sitting position)
  • Clinically unstable coronary artery disease or major cardiovascular or neurological event in the past 6 months.
  • Any other significant systemic, hepatic, cardiac or renal illness
  • Use of MAO-I (i.e. selegiline; rasagiline - Azilect, linezolid and others) within 14 days
  • Known closed-angle glaucoma
  • Clinically meaningful arrhythmias
  • Other factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies or an unpredictable schedule

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Related Publications (8)

  • Jordan J, Shannon JR, Grogan E, Biaggioni I, Robertson D. A potent pressor response elicited by drinking water. Lancet. 1999 Feb 27;353(9154):723. doi: 10.1016/S0140-6736(99)99015-3. No abstract available.

    PMID: 10073520BACKGROUND

  • Jordan J, Shannon JR, Black BK, Ali Y, Farley M, Costa F, Diedrich A, Robertson RM, Biaggioni I, Robertson D. The pressor response to water drinking in humans : a sympathetic reflex? Circulation. 2000 Feb 8;101(5):504-9. doi: 10.1161/01.cir.101.5.504.

    PMID: 10662747BACKGROUND

  • Jordan J, Shannon JR, Diedrich A, Black B, Robertson D, Biaggioni I. Water potentiates the pressor effect of ephedra alkaloids. Circulation. 2004 Apr 20;109(15):1823-5. doi: 10.1161/01.CIR.0000126283.99195.37. Epub 2004 Apr 5.

    PMID: 15066944BACKGROUND

  • Kobayashi S, Endou M, Sakuraya F, Matsuda N, Zhang XH, Azuma M, Echigo N, Kemmotsu O, Hattori Y, Gando S. The sympathomimetic actions of l-ephedrine and d-pseudoephedrine: direct receptor activation or norepinephrine release? Anesth Analg. 2003 Nov;97(5):1239-1245. doi: 10.1213/01.ANE.0000092917.96558.3C.

    PMID: 14570629BACKGROUND

  • Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, Birkes J, Young R, Glennon RA. In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates. J Pharmacol Exp Ther. 2003 Oct;307(1):138-45. doi: 10.1124/jpet.103.053975. Epub 2003 Sep 3.

    PMID: 12954796BACKGROUND

  • Lu CC, Diedrich A, Tung CS, Paranjape SY, Harris PA, Byrne DW, Jordan J, Robertson D. Water ingestion as prophylaxis against syncope. Circulation. 2003 Nov 25;108(21):2660-5. doi: 10.1161/01.CIR.0000101966.24899.CB. Epub 2003 Nov 17.

    PMID: 14623807BACKGROUND

  • Kanfer I, Dowse R, Vuma V. Pharmacokinetics of oral decongestants. Pharmacotherapy. 1993 Nov-Dec;13(6 Pt 2):116S-128S; discussion 143S-146S.

    PMID: 7507589BACKGROUND

  • Dupont WD, Plummer WD Jr. Power and sample size calculations. A review and computer program. Control Clin Trials. 1990 Apr;11(2):116-28. doi: 10.1016/0197-2456(90)90005-m.

    PMID: 2161310BACKGROUND

MeSH Terms

Conditions

Shy-Drager SyndromeMultiple System AtrophyPure Autonomic Failure

Interventions

PseudoephedrineWaterDrinking Water

Condition Hierarchy (Ancestors)

Primary DysautonomiasAutonomic Nervous System DiseasesNervous System DiseasesBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesMovement DisordersHypotensionVascular DiseasesCardiovascular DiseasesSynucleinopathiesNeurodegenerative Diseases

Intervention Hierarchy (Ancestors)

PropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesPhenethylaminesEthylaminesHydroxidesAlkaliesInorganic ChemicalsAnionsIonsElectrolytesOxidesOxygen CompoundsBeveragesDiet, Food, and NutritionPhysiological PhenomenaFood and Beverages

Study Officials

  • Emily M Garland, PhD, MSCI

    Vanderbilt University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Research Associate Professor

Study Record Dates

First Submitted

May 26, 2014

First Posted

May 29, 2014

Study Start

October 1, 2014

Primary Completion

December 1, 2020

Study Completion

December 1, 2020

Last Updated

May 5, 2021

Record last verified: 2021-04

Locations

US(1)