Efficacy and Safety of Midodrine and Atomoxetine for Neurogenic OH

Neurogenic Orthostatic Hypotension Clinical Trial

Official title:

Efficacy and Safety of Midodrine and Atomoxetine Treatment in Patients With Neurogenic Orthostatic Hypotension : A Prospective Randomized Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03350659
• Other study ID #: 1710-060-893
• Status: Completed
• Phase: Phase 4
• Start date: January 1, 2018
• Est. completion date: March 15, 2019

Study information

• Verified date: April 2019
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 15, 2019
• Est. primary completion date: January 29, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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:

• 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

Related Conditions & MeSH terms

• Hypotension
• Hypotension, Orthostatic
• Neurogenic Orthostatic Hypotension

Intervention

Drug:
• Midodrine
Midodrine single 5mg/day
• Atomoxetine
Atomoxetine single 18mg/day

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Kyung Hee University Hospital at Gangdong

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (11)

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Izcovich A, González 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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

Smit AA, Halliwill JR, Low PA, Wieling W. Pathophysiological basis of orthostatic hypotension in autonomic failure. J Physiol. 1999 Aug 15;519 Pt 1:1-10. Review. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	after 3-month medical treatment
Secondary	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.	after 3-month medical treatment
Secondary	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	after 3-month medical treatment
Secondary	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.	after 3-month medical treatment