Trial Outcomes & Findings for Effects of Caffeine and Intermittent Hypoxia on Leg Function in Human Spinal Cord Injury (NCT NCT02323698)
NCT ID: NCT02323698
Last Updated: 2023-12-13
Results Overview
Speed will be assessed using the time required to walk 10 meters (10MWT) relative to baseline.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
36 participants
Primary outcome timeframe
Baseline, after intervention (day 5), and at follow-ups (one week and two weeks)
Results posted on
2023-12-13
Participant Flow
Participant milestones
| Measure |
Caffeine/AIH First, Then Placebo/AIH, Then Caffeine/SHAM
Subjects ingest Caffeine/Placebo 30 minutes prior to AIH/SHAM breathing intervention in this cross-over study. All participants are assigned to receive all three intervention combinations of Caffeine/AIH, Placebo/AIH, and Caffeine/SHAM in a randomized order with each intervention lasting 5 days followed by 14 days of washout prior to starting the next intervention. Throughout experimentation, blood oxygenation, blood pressure and heart rate are monitored.
Caffeine: Subjects ingest capsules containing caffeine (up to 6mg/kg). Breathing intervention begins 30min after consumption to approximately coincide with peak plasma concentrations.
Placebo: This is a placebo counterpart to the caffeine drug. Subjects ingest capsules containing dextrose. Breathing intervention begins 30min after consumption to mimic the caffeine drug protocol.
AIH: Participants breathe intermittent low oxygen via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure intermittent delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia) at 1-minute intervals.
SHAM: This is a placebo counterpart to breathing intermittent low oxygen. Participants breathe intermittent room air via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.21±0.02 (normoxia).
|
Placebo/AIH First, Then Caffeine/AIH, Then Caffeine/SHAM
Subjects ingest Caffeine/Placebo 30 minutes prior to AIH/SHAM breathing intervention in this cross-over study. All participants are assigned to receive all three intervention combinations of Caffeine/AIH, Placebo/AIH, and Caffeine/SHAM in a randomized order with each intervention lasting 5 days followed by 14 days of washout prior to starting the next intervention. Throughout experimentation, blood oxygenation, blood pressure and heart rate are monitored.
Caffeine: Subjects ingest capsules containing caffeine (up to 6mg/kg). Breathing intervention begins 30min after consumption to approximately coincide with peak plasma concentrations.
Placebo: This is a placebo counterpart to the caffeine drug. Subjects ingest capsules containing dextrose. Breathing intervention begins 30min after consumption to mimic the caffeine drug protocol.
AIH: Participants breathe intermittent low oxygen via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure intermittent delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia) at 1-minute intervals.
SHAM: This is a placebo counterpart to breathing intermittent low oxygen. Participants breathe intermittent room air via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.21±0.02 (normoxia).
|
Caffeine/SHAM First, Then Caffeine/AIH, Then Placebo/AIH
Subjects ingest Caffeine/Placebo 30 minutes prior to AIH/SHAM breathing intervention in this cross-over study. All participants are assigned to receive all three intervention combinations of Caffeine/AIH, Placebo/AIH, and Caffeine/SHAM in a randomized order with each intervention lasting 5 days followed by 14 days of washout prior to starting the next intervention. Throughout experimentation, blood oxygenation, blood pressure and heart rate are monitored.
Caffeine: Subjects ingest capsules containing caffeine (up to 6mg/kg). Breathing intervention begins 30min after consumption to approximately coincide with peak plasma concentrations.
Placebo: This is a placebo counterpart to the caffeine drug. Subjects ingest capsules containing dextrose. Breathing intervention begins 30min after consumption to mimic the caffeine drug protocol.
AIH: Participants breathe intermittent low oxygen via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure intermittent delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia) at 1-minute intervals.
SHAM: This is a placebo counterpart to breathing intermittent low oxygen. Participants breathe intermittent room air via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.21±0.02 (normoxia).
|
Caffeine/AIH First, Then Caffeine/SHAM, Then Placebo/AIH
Subjects ingest Caffeine/Placebo 30 minutes prior to AIH/SHAM breathing intervention in this cross-over study. All participants are assigned to receive all three intervention combinations of Caffeine/AIH, Placebo/AIH, and Caffeine/SHAM in a randomized order with each intervention lasting 5 days followed by 14 days of washout prior to starting the next intervention. Throughout experimentation, blood oxygenation, blood pressure and heart rate are monitored.
Caffeine: Subjects ingest capsules containing caffeine (up to 6mg/kg). Breathing intervention begins 30min after consumption to approximately coincide with peak plasma concentrations.
Placebo: This is a placebo counterpart to the caffeine drug. Subjects ingest capsules containing dextrose. Breathing intervention begins 30min after consumption to mimic the caffeine drug protocol.
AIH: Participants breathe intermittent low oxygen via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure intermittent delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia) at 1-minute intervals.
SHAM: This is a placebo counterpart to breathing intermittent low oxygen. Participants breathe intermittent room air via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.21±0.02 (normoxia).
|
Placebo/AIH First, Then Caffeine/SHAM, Then Caffeine/AIH
Subjects ingest Caffeine/Placebo 30 minutes prior to AIH/SHAM breathing intervention in this cross-over study. All participants are assigned to receive all three intervention combinations of Caffeine/AIH, Placebo/AIH, and Caffeine/SHAM in a randomized order with each intervention lasting 5 days followed by 14 days of washout prior to starting the next intervention. Throughout experimentation, blood oxygenation, blood pressure and heart rate are monitored.
Caffeine: Subjects ingest capsules containing caffeine (up to 6mg/kg). Breathing intervention begins 30min after consumption to approximately coincide with peak plasma concentrations.
Placebo: This is a placebo counterpart to the caffeine drug. Subjects ingest capsules containing dextrose. Breathing intervention begins 30min after consumption to mimic the caffeine drug protocol.
AIH: Participants breathe intermittent low oxygen via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure intermittent delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia) at 1-minute intervals.
SHAM: This is a placebo counterpart to breathing intermittent low oxygen. Participants breathe intermittent room air via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.21±0.02 (normoxia).
|
Caffeine/SHAM First, Then Placebo/AIH, Then Caffeine/AIH
Subjects ingest Caffeine/Placebo 30 minutes prior to AIH/SHAM breathing intervention in this cross-over study. All participants are assigned to receive all three intervention combinations of Caffeine/AIH, Placebo/AIH, and Caffeine/SHAM in a randomized order with each intervention lasting 5 days followed by 14 days of washout prior to starting the next intervention. Throughout experimentation, blood oxygenation, blood pressure and heart rate are monitored.
Caffeine: Subjects ingest capsules containing caffeine (up to 6mg/kg). Breathing intervention begins 30min after consumption to approximately coincide with peak plasma concentrations.
Placebo: This is a placebo counterpart to the caffeine drug. Subjects ingest capsules containing dextrose. Breathing intervention begins 30min after consumption to mimic the caffeine drug protocol.
AIH: Participants breathe intermittent low oxygen via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure intermittent delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia) at 1-minute intervals.
SHAM: This is a placebo counterpart to breathing intermittent low oxygen. Participants breathe intermittent room air via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.21±0.02 (normoxia).
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Overall Study
Completed First Intervention (5 Days)
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Overall Study
Completed Second Intervention (5 Days)
|
2
|
2
|
1
|
2
|
2
|
2
|
|
Overall Study
Completed Third Intervention (5 Days)
|
2
|
2
|
0
|
2
|
1
|
2
|
|
Overall Study
COMPLETED
|
2
|
2
|
0
|
2
|
1
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
2
|
0
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
All Study Participants
n=12 Participants
Subjects ingest Caffeine/Placebo 30 minutes prior to AIH/SHAM breathing intervention in this cross-over study. All participants are assigned to receive all three intervention combinations of Caffeine/AIH, Placebo/AIH, and Caffeine/SHAM in a randomized order with each intervention lasting 5 days followed by 14 days of washout prior to starting the next intervention. Throughout experimentation, blood oxygenation, blood pressure and heart rate are monitored.
Caffeine: Subjects ingest capsules containing caffeine (up to 6mg/kg). Breathing intervention begins 30min after consumption to approximately coincide with peak plasma concentrations.
Placebo: This is a placebo counterpart to the caffeine drug. Subjects ingest capsules containing dextrose. Breathing intervention begins 30min after consumption to mimic the caffeine drug protocol.
AIH: Participants breathe intermittent low oxygen via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure intermittent delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia) at 1-minute intervals.
SHAM: This is a placebo counterpart to breathing intermittent low oxygen. Participants breathe intermittent room air via air generators. The generators fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration is continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.21±0.02 (normoxia).
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=12 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=12 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=12 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=12 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=12 Participants
|
|
Number of Participants with Level of Spinal Cord Injury (C2-L5)
|
10 Participants
n=12 Participants
|
|
Time Since Injury
|
8 years
STANDARD_DEVIATION 12 • n=12 Participants
|
|
CYP1A2*1F SNP
A/A
|
3 participants
n=12 Participants
|
|
CYP1A2*1F SNP
C/A
|
8 participants
n=12 Participants
|
|
10 Meter Walk Test
|
32.8 Seconds
STANDARD_DEVIATION 31.0 • n=12 Participants
|
PRIMARY outcome
Timeframe: Baseline, after intervention (day 5), and at follow-ups (one week and two weeks)Speed will be assessed using the time required to walk 10 meters (10MWT) relative to baseline.
Outcome measures
| Measure |
Caffeine/AIH
n=10 Participants
Subjects with chronic, motor-incomplete SCI receive Caffeine then AIH
Caffeine: Subjects will ingest capsules containing caffeine (up to 6mg/kg). Experiments will begin 30min after consumption to approximately coincide with peak plasma concentrations.Throughout the 30min wait time and experimentation, blood pressure and heart rate will be monitored.
AIH: Participants will breathe intermittent low oxygen via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia). Throughout experimentation, blood pressure and heart rate will be monitored.
|
Placebo/AIH
n=7 Participants
Subjects with chronic, motor-incomplete SCI receive Placebo then AIH
AIH: Participants will breathe intermittent low oxygen via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia). Throughout experimentation, blood pressure and heart rate will be monitored.
Placebo: This is a placebo counterpart to the caffeine drug. Subjects will ingest capsules containing dextrose. Experiments will begin 30min after consumption to mimic the caffeine drug protocol. Throughout experimentation, blood oxygenation, blood pressure and heart rate will be monitored.
|
Caffeine/SHAM
n=10 Participants
Subjects with chronic, motor-incomplete SCI receive Caffeine then SHAM
Caffeine: Subjects will ingest capsules containing caffeine (up to 6mg/kg). Experiments will begin 30min after consumption to approximately coincide with peak plasma concentrations.Throughout the 30min wait time and experimentation, blood pressure and heart rate will be monitored.
SHAM: This is a placebo counterpart to breathing intermittent low oxygen. Participants will breathe intermittent room air via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.21±0.02 (normoxia). Throughout experimentation, blood pressure and heart rate will be monitored.
|
|---|---|---|---|
|
10 Meter Walk Time
Day 5 (Relative to Baseline)
|
-5.0 Seconds
Standard Error 2.2
|
-4.9 Seconds
Standard Error 2.2
|
-4.6 Seconds
Standard Error 2.1
|
|
10 Meter Walk Time
Day 12 (Relative to Baseline)
|
-5.5 Seconds
Standard Error 2.7
|
-1.7 Seconds
Standard Error 1.3
|
0.9 Seconds
Standard Error 1.5
|
|
10 Meter Walk Time
Day 19 (Relative to Baseline)
|
-6.5 Seconds
Standard Error 3.3
|
0.4 Seconds
Standard Error 2.6
|
-0.1 Seconds
Standard Error 0.6
|
SECONDARY outcome
Timeframe: Baseline, after intervention (day 5), and at follow-ups (one week and two weeks)Measure participant's distance walked in 6 minutes (meters).
Outcome measures
| Measure |
Caffeine/AIH
n=11 Participants
Subjects with chronic, motor-incomplete SCI receive Caffeine then AIH
Caffeine: Subjects will ingest capsules containing caffeine (up to 6mg/kg). Experiments will begin 30min after consumption to approximately coincide with peak plasma concentrations.Throughout the 30min wait time and experimentation, blood pressure and heart rate will be monitored.
AIH: Participants will breathe intermittent low oxygen via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia). Throughout experimentation, blood pressure and heart rate will be monitored.
|
Placebo/AIH
n=12 Participants
Subjects with chronic, motor-incomplete SCI receive Placebo then AIH
AIH: Participants will breathe intermittent low oxygen via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia). Throughout experimentation, blood pressure and heart rate will be monitored.
Placebo: This is a placebo counterpart to the caffeine drug. Subjects will ingest capsules containing dextrose. Experiments will begin 30min after consumption to mimic the caffeine drug protocol. Throughout experimentation, blood oxygenation, blood pressure and heart rate will be monitored.
|
Caffeine/SHAM
n=8 Participants
Subjects with chronic, motor-incomplete SCI receive Caffeine then SHAM
Caffeine: Subjects will ingest capsules containing caffeine (up to 6mg/kg). Experiments will begin 30min after consumption to approximately coincide with peak plasma concentrations.Throughout the 30min wait time and experimentation, blood pressure and heart rate will be monitored.
SHAM: This is a placebo counterpart to breathing intermittent low oxygen. Participants will breathe intermittent room air via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.21±0.02 (normoxia). Throughout experimentation, blood pressure and heart rate will be monitored.
|
|---|---|---|---|
|
6 Minute Walk Test
Day 5 (Relative to Baseline)
|
24.1 Meters
Standard Error 8.3
|
17.1 Meters
Standard Error 7.3
|
6.2 Meters
Standard Error 8.7
|
|
6 Minute Walk Test
Day 12 (Relative to Baseline)
|
23.7 Meters
Standard Error 7.7
|
15.7 Meters
Standard Error 7.3
|
9.2 Meters
Standard Error 9.3
|
|
6 Minute Walk Test
Day 19 (Relative to Baseline)
|
22.4 Meters
Standard Error 8.0
|
24.2 Meters
Standard Error 7.6
|
-2.7 Meters
Standard Error 8.8
|
Adverse Events
Caffeine/AIH
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo/AIH
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Caffeine/SHAM
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr. Randy D Trumbower, PI
Spaulding Rehabilitation Hospital
Phone: (617) 952-6953
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place