Double-blinded, placebo-controlled crossover trial to determine the effects of midodrine on blood pressure during cognitive testing in persons with SCI


Study design

Clinical trial.


Individuals with spinal cord injury (SCI) above T6 experience impaired descending cortical control of the autonomic nervous system, which predisposes them to hypotension. However, treatment of hypotension is uncommon in the SCI population because there are few safe and effective pharmacological options available. The primary aim of this investigation was to test the efficacy of a single dose of midodrine (10 mg), compared with placebo, to increase and normalize systolic blood pressure (SBP) between 110 and 120 mmHg during cognitive testing in hypotensive individuals with SCI. Secondary aims were to determine the effects of midodrine on cerebral blood flow velocity (CBFv) and global cognitive function.


United States clinical research laboratory.


Forty-one healthy hypotensive individuals with chronic (≥1-year post injury) SCI participated in this 2-day study. Seated SBP, CBFv, and cognitive performance were monitored before and after administration of identical encapsulated tablets, containing either midodrine or placebo.


Compared with placebo, midodrine increased SBP (4 ± 13 vs. 18 ± 24 mmHg, respectively; p < 0.05); however, responses varied widely with midodrine (−15.7 to +68.6 mmHg). Further, the proportion of SBP recordings within the normotensive range did not improve during cognitive testing with midodrine compared with placebo. Although higher SBP was associated with higher CBFv (p = 0.02), global cognitive function was not improved with midodrine.


The findings indicate that midodrine increases SBP and may be beneficial in some hypotensive patients with SCI; however, large heterogeneity of responses to midodrine suggests careful monitoring of patients following administration.

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Fig. 1: Resting systemic and cerebral hemodynamic responses to placebo and midodrine.
Fig. 2: Relationship between change in SBP and change in MFV.
Fig. 3: Systolic blood pressure following placebo and midodrine.
Fig. 4: Stability of systolic blood pressure during cognitive testing before and after midodrine.

Data availability

The data sets generated and analyzed in the current study are available from the corresponding authors upon request.


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We would like to thank all the study participants for their involvement in this study and want to acknowledge Beatrice Ugiliweneza, Samineh Mesbah and Susan Harkema for their programming and statistical skills in creating the area-under-the-curve analyses.


This project was funded by the Craig H Neilsen Foundation (Grant #284196) and the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service Center for the Medical Consequences of Spinal Cord Injury (Grants #D1382-P and #B2020-C).

Author information




JMW oversaw and was primarily responsible for designing the study, participant enrollment, data collection procedures, database management, data analysis, result dissemination, and regulation compliance; JPW was primarily responsible for designing the study, data analysis, and result dissemination; CGK was primarily responsible for participant enrollment, data collection procedures, database management, and regulation compliance; NDC oversaw study design pertaining to the cognitive outcomes and was primarily responsible for the cognitive data analyses; SCK was responsible for monitoring patient safety at the Kessler Foundation; TAD was responsible for participant enrollment and monitoring patient safety at the Kessler Foundation; EW was responsible for analysis of the cognitive outcomes; WAB monitored patient safety at the VA and oversaw data analysis and result dissemination.

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Correspondence to Jill M. Wecht.

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Wecht, J.M., Weir, J.P., Katzelnick, C.G. et al. Double-blinded, placebo-controlled crossover trial to determine the effects of midodrine on blood pressure during cognitive testing in persons with SCI. Spinal Cord 58, 959–969 (2020).

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