The goal of this trial is to study if the concomitant administration of Telmisartan, Cilostazol IR (immediate release), and Metformin ER (extended release) can help stroke survivors make greater gains in movement and recovery during robot-assisted arm and hand rehabilitation.

The overall objective of the proposed study is to assess the viability of a pharmacotherapy combining Telmisartan, Cilostazol IR, and Metformin ER to affect the motor gains achieved via robot-assisted (RA) upper-extremity (UE) rehabilitation in stroke survivors. The hypothesis underlying the study design is that concomitant administration of Telmisartan, Cilostazol IR, and Metformin ER (herein referred to as "the proposed pharmacotherapy") leads to enhancing motor and non-motor gains observed in stroke survivors in response to RA UE rehabilitation. Participants will take these medications either once a day (QD) or twice a day (BID) as described in the protocol.

To test this hypothesis, we plan to accomplish the following primary and secondary aims.

Primary Aims:

• 1 To determine if administration of the proposed pharmacotherapy in combination with RA UE rehabilitation leads to greater improvements in UE motor impairment than previously observed in clinical trials relying on RA UE rehabilitation alone.
• 2 To evaluate potential adverse events when using the proposed pharmacotherapy in combination with RA UE rehabilitation.

Secondary Aim:

#1 To determine if the proposed pharmacotherapy in combination with RA UE rehabilitation improves UE functional ability, health related quality of life, and cognition.

Exploratory Aims:

• 1 To determine the association between response to the proposed pharmacotherapy and serum-based biomarkers collected at baseline (i.e., evaluation session prior to training), during the first training session (beginning and end of the session), during the last training session (beginning and end of the session), and during the 3-month follow-up evaluation session.
• 2 To evaluate the retention of motor and cognitive gains at 1-month post-intervention.

Inclusion Criteria:

• Adults between 21 and 80 years of age.
• History of ischemic stroke.
• Stroke occurred at least six months prior to recruitment.
• Moderate to severe UE impairment (FMA-UE score between 15 and 40)
• MMSE score >=20 and being able to safely follow three-step commands.

Exclusion Criteria:

• Contraindications to the pharmacotherapy (e.g., heart failure, known medication reaction or interactions with ongoing medication regimen).
• Taking dual antiplatelet therapy (e.g., Aspirin+Plavix) and/or other anticoagulation medications (e.g., Eliquis, coumadin) that cannot safely be modified or discontinued (as determined by the participant's primary care physician or by the medical monitor).
• Clinically significant somnolence and/or depression that would hinder active participation in motor training sessions.
• Taking any medication that the study physician determines to have a significant drug-drug interaction with Telmisartan, Cilostazol, and/or Metformin.
• Taking Telmisartan, Cilostazol, and/or Metformin in a dose that is different from the one used in the study and that cannot be adjusted to match the study dose (as determined by the participant's primary care physician or by the medical monitor).
• Taking medications with equivalent clinical effect (e.g., BP control) to Telmisartan, Cilostazol, and/or Metformin and that cannot be replaced by Telmisartan, Cilostazol, and/or Metformin (as determined by the participant's primary care physician or by the medical monitor).
• A body mass index (BMI) below 25 (as the proposed pharmacotherapy could cause hypoglycemia in participants with normal-low BMI).
• Severe musculoskeletal pathology or recent fractures affecting the impaired UE that would prevent safe use of the rehabilitation robotic system.
• Previous diagnosis of neurological diseases other than stroke that would have a negative impact on the response to the rehabilitation intervention (e.g., severe dystonia affecting the UE) or would prevent safe participation in RA UE training (e.g., uncontrolled seizures).
• Moderate to severe disability due to migraines as determined using the Migraine Disability Assessment test (score > 10).
• Severe spasticity (Modified Ashworth Scale for spasticity ≥ 3 for UE muscles) that would prevent safe use of the robotic system utilized during training.
• Undergoing Botox treatment for pain/spasticity related to the affected upper extremity, in the 4 months prior to enrollment or during the study period.
• Cerebellar and/or hemorrhagic stroke.
• Severe aphasia limiting the ability to express needs or discomfort verbally or non-verbally.
• Visual impairments that would prevent proper use of interactive on-screen games during RA UE training.
• Severe hemispatial neglect as assessed using the Line Bisection Test (missed lines >2).
• Severely impaired trunk control that would prevent sitting safely on a chair without arms.
• Individuals who present with the following on the impaired UE: open wounds, fragile skin, and under contact precautions due to an active infection.
• Participation in another therapy focused on the recovery of the impaired UE.
• Subjects with cardiac pacemakers, electronic pumps, or any other implanted medical devices that are not US-certified (and hence might be affected by the electromagnetic interference generated by the robot).
• Any condition that would prevent proper/safe use of the robotic system, such as proprioceptive deficits that impair the ability to process haptic or visual feedback, or unstable shoulder joint as assessed by physical examination.
• Current pregnancy.

Primary and secondary outcome measures will be shared via publications (de-identified individual participant data will be included in the Supplementary Materials section of the manuscript).

At the time of publication of the manuscript summarizing the results of the study. De-identified individual participant data will be included in the Supplementary Materials section of the manuscript

We plan to publish an open access manuscript summarizing the results of the study and providing (in the Supplementary Materials section of the manuscript) de-identified individual participant data. Hence, de-identified individual participant data will be accessible by the public at large.