PROGRESS: Clinical Evaluation of the Infinity Deep Brain Stimulation System

• Sponsor: Abbott Medical Devices (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02989610
• Collaborator: (none)
• Enrollment: 234
• Locations: 49
• Arm: 1
• Actual Duration (Months): 62.6
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this post-market study is to characterize the clinical performance of the Infinity Deep Brain Stimulation (DBS) system, including the Implantable Pulse Generator (IPG), directional DBS leads, extensions, iPad clinician programmer, iPod patient controller and related system components.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Device: Omnidirectional stimulation; Device: Directional stimulation	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 234 participants
• Allocation: N/A
• Intervention Model: Crossover Assignment
• Intervention Model Description: Single-arm crossover study, with double-blind, randomized sequence of testing for primary endpoint. Although this was a crossover study, the primary endpoint was a double-blind randomized controlled assessment of therapeutic window during the 3-month clinic visit. Subjects received both directional and omnidirectional stimulation, and the order was randomized.Single-arm crossover study, with double-blind, randomized sequence of testing for primary endpoint. Although this was a crossover study, the primary endpoint was a double-blind randomized controlled assessment of therapeutic window during the 3-month clinic visit. Subjects received both directional and omnidirectional stimulation, and the order was randomized.
• Masking: None (Open Label)
• Masking Description: Single-arm, open-label design for overall study. Primary endpoint is based on double-blind, randomized testing of omnidirectional and directional DBS during three-month follow visit. Participants are blinded to all details of stimulation for first six months, including details of stimulation testing. Outcomes assessor is blinded to stimulation type for primary and secondary endpoints.
• Primary Purpose: Treatment
• Official Title: Post Market Clinical Follow Up Evaluating the Infinity Deep Brain Stimulation Implantable Pulse Generator System
• Actual Study Start Date: Jan 31, 2017
• Actual Primary Completion Date: Aug 7, 2019
• Actual Study Completion Date: Apr 19, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Omnidirectional followed by directional DBS Omnidirectional DBS is used for the first 3 months in all subjects, unless not tolerated. Directional DBS is used for months 3-6 in all subjects with a directional DBS lead. Primary endpoint is based on double-blind testing of omnidirectional vs. directional DBS in randomized order at 3-month follow-up visit.

Device: Omnidirectional stimulation; At the 3-month follow-up, therapeutic window, symptom relief and side effect thresholds are evaluated at the best level for omnidirectional stimulation with the Infinity DBS lead.; Device: Directional stimulation; At the 3-month follow-up, therapeutic window, symptom relief and side effect thresholds are evaluated using directional contacts at the best segmented level of the Infinity DBS lead.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Wider Therapeutic Window With Directional Programming (Superiority) [3-month follow-up visit after initial programming]

   Therapeutic window is the range of stimulation amplitude that produces symptom relief without causing side effects. Proportion of subjects with a wider therapeutic window using directional stimulation, compared to a threshold of 60%. Based on randomized, double-blind evaluation using within-subject control.

Secondary Outcome Measures

1. Percentage of Participants With Wider Therapeutic Window With Directional Programming (Non-inferiority) [3-month follow-up visit after initial programming]

   Therapeutic window is the range of stimulation amplitude that produces symptom relief without causing side effects. The proportion of subjects with wider therapeutic window using directional stimulation will be compared to a performance goal of 60% with a non-inferiority threshold of 40%. Based on randomized, double-blind evaluation using within-subject control.

2. Change in UPDRS III Score on and Off Stimulation (Medication on) at 3 and 6 Months [3-month and 6-month follow-up visits]

   Change with stimulation on vs. off in Unified Parkinson's Disease Rating Scale (UPDRS) part III motor examination at 3 months using omnidirectional stimulation, compared to 6 months using directional stimulation. UPDRS part III contains 27 questions used to measures severity of Parkinson's motor symptoms. The range of scores is 0 to 108, with higher score indicating greater symptoms. Subjects are on medication for the assessment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is able to provide informed consent;

• Subject is diagnosed with Parkinson's disease (PD) and has been recommended to receive an Infinity DBS system with a bilateral DBS implant in the Subthalamic Nucleus (STN), or has received an implant of an Infinity system with bilateral lead implants in the STN;

• Subject must be available for follow-up visits.

Exclusion Criteria:

• Subject is not a surgical candidate;

• In the investigator's opinion, the subject is unable to tolerate multiple programming sessions within a single setting;

• Subject is unable to comply with the follow-up schedule.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sacramento Medical Center	Sacramento	California	United States	94229
2	University of Colorado Hospital	Aurora	Colorado	United States	80045
3	Shands at University of Florida	Gainesville	Florida	United States	32608
4	University of Miami Hospital	Miami	Florida	United States	33136
5	Rush University, Department of Neurological Sciences	Chicago	Illinois	United States	60612
6	Kansas University Medical Center	Kansas City	Kansas	United States	66160
7	Johns Hopkins University Hospital	Baltimore	Maryland	United States	20814
8	Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08901
9	Albany Medical Center	Albany	New York	United States	12208
10	New York University Langone Medical Center	New York	New York	United States	10016
11	Mount Sinai Hospital, New York, Department of Neurology	New York	New York	United States	10029
12	Mount Sinai Hospital	New York	New York	United States	10029
13	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
14	Oregon Health & Science University	Portland	Oregon	United States	97239
15	Oregon Health and Science University, Department of Neurology	Portland	Oregon	United States	97239
16	St. Luke's Hospital & Health Network	Bethlehem	Pennsylvania	United States	18018
17	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19104
18	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
19	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15243
20	Neurology Consultants of Dallas	Dallas	Texas	United States	75251
21	CHI St. Luke's Health Baylor College	Houston	Texas	United States	77030
22	Abbott, Medical and Clinical Affairs	Plano	Texas	United States	75024
23	Princess Alexandra Hospital	Brisbane		Australia	4102
24	Royal Melbourne Hospital, Department of Neurology	Melbourne		Australia	3050
25	Royal Melbourne Hospital	Melbourne		Australia	3050
26	Westmead Hospital	Richmond		Australia	2145
27	UZ Gent	Gent		Belgium
28	Johannes Gutenberg University of Mainz, Department of Neurosurgery	Mainz,	Mainz	Germany	55126
29	Universitätsklinikum Carl Gustav Carus Dresden	Dresden		Germany	1815
30	Heinrich Heine University of Düsseldorf, Department of Neurology	Düsseldorf,		Germany	40210
31	Heinrich Heine University of Düsseldorf, Department of Neurology	Düsseldorf		Germany	40210
32	Heinrich Heine University of Düsseldorf, Department of Neurosurgery	Düsseldorf		Germany	40210
33	Heinrich Heine University of Düsseldorf, Department of Neurology	Düsseldorf		Germany	40225
34	Medizinische Einrichtungen der Universität Düsseldorf	Düsseldorf		Germany
35	University Medical Centre Hamburg, Department of Neurology,	Hamburg		Germany	20251
36	UKE Hamburg	Hamburg		Germany
37	Johannes Gutenberg-University of Mainz	Mainz		Germany
38	Klinikum der Universität Regensburg	Regensburg		Germany
39	IRCCS Istituto Ortopedico Galeazzi	Milano		Italy
40	Fondazione Istituto Neurologico Nazionale C. Mondino	Pavia		Italy
41	Azienda Ospedaliero-Universitaria S Maria della Misericordia	Udine		Italy
42	Copernicus Hospital, Department of Neurosurgery,	Gdańsk		Poland
43	Institute of Psychiatry and Neurology	Warsaw		Poland
44	Hospital Trias i Pujol, Department of Neurology	Badalona		Spain	08917
45	Hospital Trias i Pujol	Badalona		Spain	08917
46	Hospital Universitario Central de Asturias	Oviedo		Spain	32762
47	Hospital Universitario Central de Asturias, Department of Neurology,	Oviedo		Spain	33011
48	Hospital Universitario Virgen del Rocío, Department of Neurology	Sevilla		Spain	41013
49	Hospital Universitario Virgen del Rocío, Department of Neurology	Sevilla		Spain

Sponsors and Collaborators

• Abbott Medical Devices

Investigators

• Principal Investigator: Alfons Schnitzler, MD, Heinrich-Heine-Universität Düsseldorf, Institute for Clinical Neuroscience
• Principal Investigator: Jan Vesper, MD, Heinrich-Heine-Universität Düsseldorf, Department of Functional and Stereotactic Neurosurgery

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 23, 2019

More Information

Publications

None provided.

• Responsible Party: Abbott Medical Devices
• ClinicalTrials.gov Identifier: NCT02989610
• Other Study ID Numbers: SJM-CIP-10061
• First Posted: Dec 12, 2016
• Last Update Posted: Jul 14, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Parkinson Disease

Study Results

Participant Flow

Recruitment Details	The PROGRESS study enrolled a total of 234 participants between January 2017 and January 2019 at 37 sites in Europe, the U.S. and Australia. Of which 195 participants completed 6 months follow-up visit.
Pre-assignment Detail	Of the 234 enrolled participants, there were 230 participants who had initial study programming. Out of 212 participants who completed the 3-month visit, there were 202 with complete primary endpoint data. After the 3-month visit, 17 were withdrawn or lost to follow-up, leaving the number of participants completed as of 195 participants.

Arm/Group Title	Omnidirectional Followed by Directional DBS
Arm/Group Description	Omnidirectional DBS is used for the first 3 months in all subjects, unless not tolerated. Directional DBS is used for the following three months up to 6 months, unless not tolerated. At the three and twelve month follow-up visit therapeutic window, symptom relief and side effect thresholds are evaluated at the best level for omnidirectional and directional stimulation with the Infinity DBS lead.
Period Title: Overall Study
STARTED	234
COMPLETED	195
NOT COMPLETED	39

Baseline Characteristics

Arm/Group Title	Omnidirectional Followed by Directional DBS
Arm/Group Description	Omnidirectional DBS is used for the first 3 months in all subjects, unless not tolerated. Directional DBS is used for the following three months up to 6 months, unless not tolerated. At the three and twelve month follow-up visit therapeutic window, symptom relief and side effect thresholds are evaluated at the best level for omnidirectional and directional stimulation with the Infinity DBS lead.
Overall Participants	234
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.7 (8.4)
Sex: Female, Male (Count of Participants)
Female	77 32.9%
Male	157 67.1%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Number) [Number]
United States	90 38.5%
Italy	4 1.7%
Germany	62 26.5%
Spain	43 18.4%
Australia	15 6.4%
Poland	19 8.1%
Belgium	1 0.4%
Duration of Parkinson Symptoms (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	11.7 (7.6)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Wider Therapeutic Window With Directional Programming (Superiority)
Description	Therapeutic window is the range of stimulation amplitude that produces symptom relief without causing side effects. Proportion of subjects with a wider therapeutic window using directional stimulation, compared to a threshold of 60%. Based on randomized, double-blind evaluation using within-subject control.
Time Frame	3-month follow-up visit after initial programming

Outcome Measure Data

Analysis Population Description

The number of participants analyzed includes subjects for whom data were available at that time of analysis.

Arm/Group Title	Omnidirectional Followed by Directional DBS
Arm/Group Description	Omnidirectional DBS is used for the first 3 months in all subjects, unless not tolerated. Directional DBS is used for the following three months up to 6 months, unless not tolerated. At the three and twelve month follow-up visit therapeutic window, symptom relief and side effect thresholds are evaluated at the best level for omnidirectional and directional stimulation with the Infinity DBS lead.
Measure Participants	66
Count of Participants [Participants]	59 25.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omnidirectional Followed by Directional DBS
	Comments	Proportion with wider therapeutic window using directional stimulation was compared to a performance goal of 60%.
	Type of Statistical Test	Superiority
	Comments	Superiority hypothesis was that 95% lower confidence bound on proportion exceeded a threshold of 60%.
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Clopper-Pearson method
	Comments

2. Secondary Outcome

Title	Percentage of Participants With Wider Therapeutic Window With Directional Programming (Non-inferiority)
Description	Therapeutic window is the range of stimulation amplitude that produces symptom relief without causing side effects. The proportion of subjects with wider therapeutic window using directional stimulation will be compared to a performance goal of 60% with a non-inferiority threshold of 40%. Based on randomized, double-blind evaluation using within-subject control.
Time Frame	3-month follow-up visit after initial programming

Outcome Measure Data

Analysis Population Description

The number of participants analyzed includes subjects for whom data were available at that time of analysis.

Arm/Group Title	Omnidirectional Followed by Directional DBS
Arm/Group Description	Omnidirectional DBS is used for the first 3 months in all subjects, unless not tolerated. Directional DBS is used for the following three months up to 6 months, unless not tolerated. At the three and twelve month follow-up visit therapeutic window, symptom relief and side effect thresholds are evaluated at the best level for omnidirectional and directional stimulation with the Infinity DBS lead.
Measure Participants	66
Count of Participants [Participants]	59 25.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omnidirectional Followed by Directional DBS
	Comments	Proportion with wider therapeutic window using directional stimulation was compared to a performance goal of 60%.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority hypothesis was that 95% lower confidence bound on proportion exceeded a threshold of 40%.
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Clopper-Pearson method
	Comments

3. Secondary Outcome

Title	Change in UPDRS III Score on and Off Stimulation (Medication on) at 3 and 6 Months
Description	Change with stimulation on vs. off in Unified Parkinson's Disease Rating Scale (UPDRS) part III motor examination at 3 months using omnidirectional stimulation, compared to 6 months using directional stimulation. UPDRS part III contains 27 questions used to measures severity of Parkinson's motor symptoms. The range of scores is 0 to 108, with higher score indicating greater symptoms. Subjects are on medication for the assessment.
Time Frame	3-month and 6-month follow-up visits

Outcome Measure Data

Analysis Population Description

The number of participants analyzed includes subjects for whom data were available at that time of analysis.

Arm/Group Title	Omnidirectional Followed by Directional DBS
Arm/Group Description	Omnidirectional DBS is used for the first 3 months in all subjects, unless not tolerated. Directional DBS is used for the following three months up to 6 months, unless not tolerated. At the three and twelve month follow-up visit therapeutic window, symptom relief and side effect thresholds are evaluated at the best level for omnidirectional and directional stimulation with the Infinity DBS lead.
Measure Participants	66
Omnidirectional stimulation (3 months)	10.6 (9.1)
Directional stimulation (6 months)	12.8 (12.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omnidirectional Followed by Directional DBS
	Comments	Comparison of UPDRS part III on medication from 3 months using omnidirectional stimulation to 6 months using directional stimulation.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	t-test, 1 sided
	Comments	Paired t-test.

Adverse Events

Time Frame	6 Months
Arm/Group Title	Omnidirectional Followed by Directional DBS
Arm/Group Description	Omnidirectional DBS is used for the first 3 months in all subjects, unless not tolerated. Directional DBS is used for the following three months up to 6 months, unless not tolerated. At the three and twelve month follow-up visit therapeutic window, symptom relief and side effect thresholds are evaluated at the best level for omnidirectional and directional stimulation with the Infinity DBS lead.
All Cause Mortality
	Omnidirectional Followed by Directional DBS
	Affected / at Risk (%)	# Events
Total	0/234 (0%)
Serious Adverse Events
	Omnidirectional Followed by Directional DBS
	Affected / at Risk (%)	# Events
Total	25/234 (10.7%)
Cardiac disorders
Mitral valve replacement	1/234 (0.4%)
Endocrine disorders
Endocrinological issues	1/234 (0.4%)
Gastrointestinal disorders
Appendicitis	1/234 (0.4%)
Umbilical hernia	1/234 (0.4%)
General disorders
Falls requiring hospitalization	1/234 (0.4%)
Infections and infestations
Sepsis secondary to influenza	1/234 (0.4%)
Injury, poisoning and procedural complications
Battery depletion resulting in hospitalization	1/234 (0.4%)
Cognitive impairment: Confusion	1/234 (0.4%)
Cognitive impairment: Disorientation	1/234 (0.4%)
Edema near site of lead	1/234 (0.4%)
Erosion	1/234 (0.4%)
Extension breakage in a swimmer	1/234 (0.4%)
Lead fracture due to trauma	1/234 (0.4%)
Loss of therapeutic benefit: Lead migration	1/234 (0.4%)
Speech or language impairment: Aphasia	1/234 (0.4%)
Speech or language impairment: Dysphagia	1/234 (0.4%)
Worsening of Parkinson's motor symptoms: Tremor	1/234 (0.4%)
Musculoskeletal and connective tissue disorders
Knee operation	1/234 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma and squamous cell carcinoma	1/234 (0.4%)
Nervous system disorders
Coma related to drowning	1/234 (0.4%)
Dopamine dysregulation syndrome	1/234 (0.4%)
Transient loss of consciousness	1/234 (0.4%)
Psychiatric disorders
Depression	1/234 (0.4%)
Skin and subcutaneous tissue disorders
Erosion related to dermatological disorder	1/234 (0.4%)
Surgical and medical procedures
Spinal cord canal stenosis	1/234 (0.4%)
Other (Not Including Serious) Adverse Events
	Omnidirectional Followed by Directional DBS
	Affected / at Risk (%)	# Events
Total	25/234 (10.7%)
Injury, poisoning and procedural complications
Worsening of Parkinson's motor symptoms: Dyskinesia	5/234 (2.1%)
Worsening of Parkinson's motor symptoms: Tremor	4/234 (1.7%)
Decreased therapeutic response	2/234 (0.9%)
Cognitive impairment: Emotional lability	2/234 (0.9%)
Sensory disturbance or impairment: Neuralgia	1/234 (0.4%)
Sensory disturbance or impairment: Sensory deficit	2/234 (0.9%)
Undesirable changes in stimulation	2/234 (0.9%)
Worsening of Parkinson's motor symptoms: Abnormal gait	2/234 (0.9%)
Worsening of Parkinson's motor symptoms: Bradykinesia	2/234 (0.9%)
Cognitive impairment: Hallucination	1/234 (0.4%)
Dystonia	1/234 (0.4%)
Erosion	1/234 (0.4%)
Impaired wound healing: Incision site drainage	1/234 (0.4%)
Sensory disturbance or impairment: Neuropathy	1/234 (0.4%)
Speech or language impairment: Dysarthria	1/234 (0.4%)
Skull discoloration	1/234 (0.4%)
Suboptimal placement of lead corrected during IPG implant	1/234 (0.4%)
High impedance	1/234 (0.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.