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CompletedNCT03350659Updated Apr 5, 2019

Efficacy and Safety of Midodrine and Atomoxetine for Neurogenic OH

A Phase 4 interventional study of Midodrine and Atomoxetine in Neurogenic Orthostatic Hypotension, sponsored by Seoul National University Hospital. Completed at 1 site in Korea, Republic of. Open to participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2019-04-05.

Sponsored by Seoul National University Hospital · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
50
Allocation
Randomized
Ages
19 Years and older
Sex
All
01

Study summary

This was a randomized, open-label clinical trial. We will enroll patients with symptomatic neurogenic OH and randomize them to 1 of 2 treatments: (1) midodrine only, (2) atomoxetine only. We will follow up patients at 1 and 3 months after treatment. If the patients meet BP criteria for OH at 1 month, they will receive combination treatment with both midodrine and atomoxetin. The primary outcome measure is amelioration of questionnaire score evaluating OH-associated symptoms at 3 months. Secondary end-points were improvement in orthostatic blood pressure (BP) drop at 1 and 3 months.

Read the detailed description

Visit 1.

  1. Enroll, baseline evaluation of the patients
  2. Questionnaire

    • Evaluate orthostatic hypotension symptom: Orthostatic Hypotension Questionnaire (OHQ)
    • Quality of life: Korean version of Short-form 36
    • Depressive symptom: Korean version of Beck Depression Inventory(BDI)-2
  3. Blood test (6cc): ELISA for alpha 1,2 and beta 1,2 adrenergic receptor antibody and nicotinic acetylcholine receptor antibody. Preserve sample for genetic testing.
  4. Randomization: randomize patients to three group in 1:1 ratio (Midodrine 5mg/day single, Atomoxetine 18mg/day single)
  5. Treatment education Visit 2. 1 month after treatment Orthostatic BP check/ check drug compliance and side effect/ Questionnaire If the patients meet BP criteria for OH, initiate combination treatment (Midodrine 5mg/day+Atomoxetine 18mg/day) Visit 3. 3 months after treatment Orthostatic BP check/ check drug compliance and side effect/ Questionnaire
02

Conditions studied

  • Neurogenic Orthostatic Hypotension

Keywords

  • orthostatic hypotension
  • midodrine
  • atomoxetine
  • treatment
03

Who can participate

Ages eligible
19 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age >=19 patients who complained of dizziness
  • Orthostatic hypotension after 3-minute standing (systolic blood pressure drop >=20 or diastolic blood pressure drop >=10

Exclusion criteria

Exclusion Criteria:

  • Drug-induced hypotension, if necessary, evaluate patient after discontinuing the causative drug for one month
  • Heart failure or Chronic renal failure
  • Severe supine hypertension (Systolic Blood Pressure >180 or Diastolic Blood Pressure>110mmHg)
  • Pregnant women, breast-feeding
  • Unable to perform questionnaire
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
50 participants (actual)

Study arms

  • Experimental
    Atomoxetine

    Atomoxetine 18mg once a day.

    Drug: Atomoxetine

  • Active comparator
    Midodrine

    midodrine 2.5mg twice a day (increase to 5mg three times a day if necessary)

    Drug: Midodrine

Interventions

  • DrugMidodrine

    Midodrine single 5mg/day

    Also known as: Midodrine only

  • DrugAtomoxetine

    Atomoxetine single 18mg/day

    Also known as: Atomoxetine only

05

What researchers measure

Primary outcomes

  1. Change of the Orthostatic Hypotension Associated Symptom Questionnaire (OH Questionnaire (OHQ)

    Change of the OH associated symptom survey result after 3-month medical treatment compared to initial results. OHQ questionnaire has two components: the OH daily activity scale (OHDAS), which contains 4 items measuring the impact of OH on daily activities, and the OH symptom assessment (OHSA), which contains 6 items measuring the symptoms of OH (dizziness/light headedness, vision disturbance, weakness, fatigue, trouble concentrating, and head/neck discomfort).This questionnaire reflects the severity of OH-related symptoms on a 10-point scale, with 0 indicating the absence of a symptom and 10 indicating maximal severity. \*\* OHQ total score minimal 0 \~ maximal 100 (subscale OHDAS score minimal 0\~ maximal 40, OHSA score minimal 0\~ maximal 60)

    Time frame: after 3-month medical treatment

Secondary outcomes

  1. Change in Orthostatic blood pressure Drop (mmHg)

    Change of orthostatic Systolic blood pressure and Diastolic Blood Pressure drop after 3-month medical treatment compared to initial results.

    Time frame: after 3-month medical treatment

  2. Change of the Depression Score (Beck Depression Inventory-II )

    Change of the depression score after 3-month medical treatment compared to initial results. 21 multiple-choice questions, each of which can be scored from 0 to 3. Higher score represent higher degree of depression. Score Normal; 0-13, Mild depression; 14-19, Moderate depression; 20-28, Severe depression; 29- 63

    Time frame: after 3-month medical treatment

  3. Changes in Health-related Quality of Life

    changes in Short Form (36) Health Survey version 2 (SF-36v2) physical component summary scale (PCS) compared to the baseline SF-36v2 measures eight HRQOL domains (physical functioning, role limitation caused by physical problems, bodily pain, general health, vitality, social functioning, role limitation caused by emotional problems, and mental health) summarized into two summary scales that are normalized to the population (mean=50, standard deviation=10): the physical component summary scale (PCS) and the mental component summary scale (MCS).20 Better HRQOL is reflected by higher SF-36v2 scores.

    Time frame: after 3-month medical treatment

06

Study locations

1 site
  • Seoul National University Hospital
    Seoul, 03080, Korea, Republic of
07

References and documents

Publications

  • Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology. 1996 May;46(5):1470. doi: 10.1212/wnl.46.5.1470. No abstract available. PubMed 8628505 ↗
  • Smit AA, Halliwill JR, Low PA, Wieling W. Pathophysiological basis of orthostatic hypotension in autonomic failure. J Physiol. 1999 Aug 15;519 Pt 1(Pt 1):1-10. doi: 10.1111/j.1469-7793.1999.0001o.x. PubMed 10432334 ↗
  • Hiitola P, Enlund H, Kettunen R, Sulkava R, Hartikainen S. Postural changes in blood pressure and the prevalence of orthostatic hypotension among home-dwelling elderly aged 75 years or older. J Hum Hypertens. 2009 Jan;23(1):33-9. doi: 10.1038/jhh.2008.81. Epub 2008 Jul 24. PubMed 18650837 ↗
  • Hale GM, Valdes J, Brenner M. The Treatment of Primary Orthostatic Hypotension. Ann Pharmacother. 2017 May;51(5):417-428. doi: 10.1177/1060028016689264. Epub 2017 Jan 16. PubMed 28092986 ↗
  • Low PA, Singer W. Management of neurogenic orthostatic hypotension: an update. Lancet Neurol. 2008 May;7(5):451-8. doi: 10.1016/S1474-4422(08)70088-7. PubMed 18420158 ↗
  • Wright RA, Kaufmann HC, Perera R, Opfer-Gehrking TL, McElligott MA, Sheng KN, Low PA. A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology. 1998 Jul;51(1):120-4. doi: 10.1212/wnl.51.1.120. PubMed 9674789 ↗
  • Parsaik AK, Singh B, Altayar O, Mascarenhas SS, Singh SK, Erwin PJ, Murad MH. Midodrine for orthostatic hypotension: a systematic review and meta-analysis of clinical trials. J Gen Intern Med. 2013 Nov;28(11):1496-503. doi: 10.1007/s11606-013-2520-3. Epub 2013 Jun 18. PubMed 23775146 ↗
  • Izcovich A, Gonzalez Malla C, Manzotti M, Catalano HN, Guyatt G. Midodrine for orthostatic hypotension and recurrent reflex syncope: A systematic review. Neurology. 2014 Sep 23;83(13):1170-7. doi: 10.1212/WNL.0000000000000815. Epub 2014 Aug 22. PubMed 25150287 ↗
  • Byun JI, Moon J, Kim DY, Shin H, Sunwoo JS, Lim JA, Kim TJ, Lee WJ, Lee HS, Jun JS, Park KI, Lee ST, Jung KH, Jung KY, Lee SK, Chu K. Efficacy of single or combined midodrine and pyridostigmine in orthostatic hypotension. Neurology. 2017 Sep 5;89(10):1078-1086. doi: 10.1212/WNL.0000000000004340. Epub 2017 Aug 9. PubMed 28794253 ↗
  • Ramirez CE, Okamoto LE, Arnold AC, Gamboa A, Diedrich A, Choi L, Raj SR, Robertson D, Biaggioni I, Shibao CA. Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. Hypertension. 2014 Dec;64(6):1235-40. doi: 10.1161/HYPERTENSIONAHA.114.04225. Epub 2014 Sep 2. PubMed 25185131 ↗
  • Hale GM, Brenner M. Atomoxetine for Orthostatic Hypotension in an Elderly Patient Over 10 Weeks: A Case Report. Pharmacotherapy. 2015 Sep;35(9):e141-8. doi: 10.1002/phar.1635. PubMed 26406777 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03350659
Lead sponsor
Seoul National University Hospital
Collaborators
Kyung Hee University Hospital at Gangdong
Responsible party
Kon Chu (Professor, Seoul National University Hospital) — Principal investigator
First posted
Nov 22, 2017
Start date
Jan 1, 2018
Primary completion
Jan 29, 2019
Completion
Mar 15, 2019
Last update
Apr 5, 2019

Study contacts

Chu Kon
principal investigator · Seoul National University Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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