Efficacy and Safety of Midodrine and Atomoxetine for Neurogenic OH

Phase 4

Completed

• Conditions: Neurogenic Orthostatic Hypotension
• Interventions: Drug: Midodrine; Drug: Atomoxetine

• Registration Number: NCT03350659
• Lead Sponsor: Seoul National University Hospital

Brief 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.

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

Study Timeline

• Study First Submitted: 2017-11-18
• Study First Submitted QC: 2017-11-18
• Study First Posted: 2017-11-22
• Study Start: 2018-01-01
• Primary Completion: 2019-01-29
• Study Completion: 2019-03-15
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-03
• Last Update Posted: 2019-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Midodrine	Midodrine	midodrine 2.5mg twice a day (increase to 5mg three times a day if necessary)
Atomoxetine	Atomoxetine	Atomoxetine 18mg once a day.

Primary Outcome Measures

Name	Time	Method
Change of the Orthostatic Hypotension Associated Symptom Questionnaire (OH Questionnaire (OHQ)	after 3-month medical treatment	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)

Secondary Outcome Measures

Name	Time	Method
Change of the Depression Score (Beck Depression Inventory-II )	after 3-month medical treatment	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
Changes in Health-related Quality of Life	after 3-month medical treatment	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.
Change in Orthostatic blood pressure Drop (mmHg)	after 3-month medical treatment	Change of orthostatic Systolic blood pressure and Diastolic Blood Pressure drop after 3-month medical treatment compared to initial results.

Trial Locations

Locations (1)

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of