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CompletedNCT06404073Updated Oct 6, 2026Results posted

RECOVER-ENERGIZE Platform Protocol_Appendix B (Structured Pacing (PEM))

An interventional study of Structured Pacing and Usual Care in Long COVID, Long Covid19 and Long Covid-19, sponsored by Duke University. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-06.

Sponsored by Duke University · Not applicable, Interventional, and Treatment

Updated Oct 6, 2026Results postedPrimary outcomes revisedGo to Updates ↓
Phase
Not applicable
Study type
Interventional
Enrollment
300
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This is a platform protocol designed to be flexible so that it is suitable for a range of interventions and settings within diverse health care systems and community settings with incorporation into clinical COVID-19 management programs and treatment plans if results achieve key study outcomes.

This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform trial evaluating interventions to address and improve exercise intolerance and post-exertional malaise (PEM) as manifestations of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC).

The focus of this protocol is to assess interventions that can improve exercise capacity, daily activities tolerance, and quality of life in patients with PASC.

Read the detailed description

Study interventions will be added to the platform protocol as appendices. Each appendix will leverage all elements of the platform protocol, with additional elements described in the individual appendix. Study intervention appendices may be added or removed according to adaptive design and/or emerging evidence.

The platform protocol enrolls participants who meet study eligibility criteria. After completing initial screening assessments, eligible participants are assigned to one of the study intervention appendices that are actively enrolling. Participants must meet certain criteria within a specific appendix in order to be included in that appendix. Once assigned to an appendix, eligible participants are randomized to either the study intervention group or a control group.

02

Conditions studied

  • Long COVID
  • Long Covid19
  • Long Covid-19

Keywords

  • PASC
  • Exercise
  • PEM (post exertional malaise)
03

In context

Post-Acute COVID-19 Syndrome

520 studies on the registry are indexed under Post-Acute COVID-19 Syndrome; 186 are open to participants now.

This study's enrollment of 300 is above the median of 60 across 361 interventional studies indexed under Post-Acute COVID-19 Syndrome.

Browse Post-Acute COVID-19 Syndrome studies →

Lead sponsor

Duke University is the lead sponsor of 2,025 studies on the registry; 275 are open to participants now.

Of its 194 completed or terminated interventional studies of FDA-regulated products, 159 (82%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

  • See NCT06404047 for RECOVER-ENERGIZE: Platform Protocol level inclusion and exclusion criteria which applies to this appendix

Additional Appendix B (Structured Pacing (PEM)) Level Inclusion Criteria:

  1. Participant identifies new PEM following a SARS-CoV-2 infection that has persisted for at least 12 weeks and is still present at the time of consent
  2. Score of 2 or greater for both frequency and severity for any of the first 5 questions on the Screening mDSQ-PEM AND Answer of YES to either item 7 or 8 on Screening mDSQ-PEM, and response of >14 h in item 9.

or Score of 3 or greater on any severity question(regardless) and answer of YES to either item 7 or 8 on the Screening mDSQ-PEM, and response of >14h in item 9.

Additional Appendix B (Structured Pacing (PEM)) Level Exclusion Criteria:

  1. Inability to attend in-person screening visit or participate in weekly visits (in-person [≥ 1] and remote)
  2. Participant was previously enrolled in Appendix A of this protocol and has NOT completed the full study follow-up period of Appendix A
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
300 participants (actual)

Study arms

  • Experimental
    Structured Pacing (PEM)

    Participants in this group will complete weekly pacing sessions for 12 weeks. Pacing sessions will last about 30 minutes, as tolerated. Each participant will meet with a provider 'pacing coach' who has received study-specific education about PEM and how to create and manage pacing strategies for participants. Sessions include PEM symptom and trigger assessment; task, function and activity analysis; adaptations and modifications.

    Behavioral: Structured Pacing

  • Other
    Usual Care

    Participants in this group will receive basic education about PEM with a weekly call by site study staff for support and communication.

    Other: Usual Care

Interventions

  • BehavioralStructured Pacing

    Participants in this group will complete weekly pacing sessions for 12 weeks. Pacing sessions will last about 30 minutes, as tolerated. Each participant will meet with a provider 'pacing coach' who has received study-specific education about PEM and how to create and manage pacing strategies for participants. Sessions include PEM symptom and trigger assessment; task, function and activity analysis; adaptations and modifications.

  • OtherUsual Care

    Participants in this group will receive basic education about PEM with a weekly call by site study staff for support and communication.

06

What researchers measure

Primary outcomes

  1. Change in Frequency of PEM Symptoms, as Measured by the Modified DePaul Symptom - Post-Exertional Malaise Questionnaire (mDSQ-PEM)

    Symptom frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time.

    Time frame: Baseline, week 12 (End Of Intervention, EOI)

  2. Change in Severity of PEM Symptoms, as Measured by the Modified DePaul Symptom - Post-Exertional Malaise Questionnaire (mDSQ-PEM)

    Symptom severity is rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe.

    Time frame: Baseline, week 12 (EOI)

  3. Change in Duration of PEM Symptoms, as Measured by the Modified DePaul Symptom - Post-Exertional Malaise Questionnaire (mDSQ-PEM)

    Ordinal categorical response: \<=1 hour, 2-3 hours, 4-10 hours, 11-13 hours, 14-23 hours, \>=24 hours. Reported as the number of participants who provided each response.

    Time frame: Baseline, week 12 (EOI)

Secondary outcomes

  1. Change in PASC Symptoms, as Measured by the PROMIS-Cog Questionnaire

    The PROMIS Short Form v.2.0 - Cognitive Function 8a (PROMIS-Cog) is the PROMIS Short Form to assess cognitive function and is a self-report, 8-item questionnaire targeting cognitive function in the past seven days. T-Scores in a healthy reference population have mean=50 and standard deviation = 10, with higher scores indicating higher functioning.

    Time frame: Baseline, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)

  2. Change in Quality of Life, as Measured by the PROMIS-29+2

    The PROMIS-29+2 is used to calculate a preference score (PROPr) by the addition of two Cognitive Function Ability items. Preference-based scores provide an overall summary of health-related quality of life on a common metric. Preference-based scores summarize multiple domains on a metric ranging from 0 (as bad as dead) to 1 (perfect or ideal health).

    Time frame: Baseline, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)

  3. Change in Quality of Life, as Measured by the EQ-5D 5L

    The EQ-5D is a standardized measure of health status. Mobility was measured on a scale from 1 (no problems in walking) to 5 (unable to walk).

    Time frame: Baseline, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)

  4. Change in Step Count (Physical Activity) as Measured by Actigraphy

    Actigraphy will be measured by Fitbit. Participant steps were considered valid from days where they wore the Fitbit at least 10 waking hours. Average steps were calculated from subjects with at least 5 consecutive days of valid data within a week window of their expected visit dates.

    Time frame: Baseline, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)

  5. Change in Physical Activity, as Measured by the PROMIS SF-Physical Function (PROMIS-PF)

    The PROMIS Short Form v2.0 - Physical Function 8b (PROMIS-PF) consists of 8 items. The PROMIS Physical Function instruments measure self-reported capability rather than actual performance of physical activities. T-Scores in a healthy reference population have mean = 50 and standard deviation = 10, with higher scores indicating higher functioning.

    Time frame: Baseline, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)

  6. Change in Orthostatic Hypotension, as Measured by the Modified Orthostatic Hypotension Questionnaire (mOHQ)

    The Orthostatic Hypotension Questionnaire (OHQ) is a measure of orthostatic intolerance. The modified OHQ (mOHQ) measure used in this study includes a total of ten items related to daily activities and symptoms. The OHQ composite score ranges from 0 (no burden) to 10 (maximal burden). Higher scores are worse. The OHQ composite score includes 6 symptom items (OISA) and 4 daily activity items (OIDAS).

    Time frame: Screening, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)

Other outcomes

  1. Change in PASC Symptoms, as Measured by the PASC Symptom Questionnaire

    The PASC Symptom Questionnaire is a 33-question survey for self-reporting multiple PASC-related symptoms across multiple systems.

    Time frame: Baseline, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)

07

Results

Posted Oct 6, 2026

Participant flow

Participant flow — Overall Study
MilestoneStructured PacingUsual Care
Started151149
Completed145144
Not completed65
Withdrew: Lost to follow-up24
Withdrew: Withdrawal by subject10
Withdrew: Ineligible due to mohq score10
Withdrew: Randomized incorrectly21

Outcome measures

PrimaryChange in Frequency of PEM Symptoms, as Measured by the Modified DePaul Symptom - Post-Exertional Malaise Questionnaire (mDSQ-PEM)

Symptom frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time.

Time frame:
Baseline, week 12 (End Of Intervention, EOI)
Reported as:
Mean · score on a scale
Change in Frequency of PEM Symptoms, as Measured by the Modified DePaul Symptom - Post-Exertional Malaise Questionnaire (mDSQ-PEM)
score on a scaleStructured PacingUsual Care
Change in Frequency of PEM Symptoms, as Measured by the Modified DePaul Symptom - Post-Exertional Malaise Questionnaire (mDSQ-PEM)-0.53 ± 1.01-0.04 ± 0.75
Statistical analysis
  • Structured Pacing vs Usual Care · Mean difference (net): -0.46 · 95% CI -0.65 to -0.27
PrimaryChange in Severity of PEM Symptoms, as Measured by the Modified DePaul Symptom - Post-Exertional Malaise Questionnaire (mDSQ-PEM)

Symptom severity is rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe.

Time frame:
Baseline, week 12 (EOI)
Reported as:
Mean · score on a scale
Change in Severity of PEM Symptoms, as Measured by the Modified DePaul Symptom - Post-Exertional Malaise Questionnaire (mDSQ-PEM)
score on a scaleStructured PacingUsual Care
Change in Severity of PEM Symptoms, as Measured by the Modified DePaul Symptom - Post-Exertional Malaise Questionnaire (mDSQ-PEM)-0.49 ± 0.900.01 ± 0.73
Statistical analysis
  • Structured Pacing vs Usual Care · Mean difference (final values): -0.47 · 95% CI -0.65 to -0.30
PrimaryChange in Duration of PEM Symptoms, as Measured by the Modified DePaul Symptom - Post-Exertional Malaise Questionnaire (mDSQ-PEM)

Ordinal categorical response: \<=1 hour, 2-3 hours, 4-10 hours, 11-13 hours, 14-23 hours, \>=24 hours. Reported as the number of participants who provided each response.

Time frame:
Baseline, week 12 (EOI)
Reported as:
Count of participants · Participants
Change in Duration of PEM Symptoms, as Measured by the Modified DePaul Symptom - Post-Exertional Malaise Questionnaire (mDSQ-PEM)
ParticipantsStructured PacingUsual Care
Baseline — <= 1 hour44
Baseline — 2-3 hours64
Baseline — 4-10 hours119
Baseline — 11-13 hours49
Baseline — 14-23 hours2626
Baseline — >= 24 hours9797
EOI — <= 1 hour52
EOI — 2-3 hours226
EOI — 4-10 hours97
EOI — 11-13 hours63
EOI — 14-23 hours2442
EOI — >= 24 hours7580
Statistical analysis
  • Structured Pacing vs Usual Care · Odds ratio (or): 0.66 · 95% CI 0.42 to 1.03Odds of higher EOI duration category for Intervention vs Placebo
SecondaryChange in PASC Symptoms, as Measured by the PROMIS-Cog Questionnaire

The PROMIS Short Form v.2.0 - Cognitive Function 8a (PROMIS-Cog) is the PROMIS Short Form to assess cognitive function and is a self-report, 8-item questionnaire targeting cognitive function in the past seven days. T-Scores in a healthy reference population have mean=50 and standard deviation = 10, with higher scores indicating higher functioning.

Time frame:
Baseline, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)
Reported as:
Mean · T-score
Change in PASC Symptoms, as Measured by the PROMIS-Cog Questionnaire
T-scoreStructured PacingUsual Care
Baseline to MOI1.26 ± 6.161.01 ± 5.50
Baseline to EOI3.08 ± 8.440.68 ± 6.77
Baseline to EOS3.02 ± 8.231.33 ± 5.94
SecondaryChange in Quality of Life, as Measured by the PROMIS-29+2

The PROMIS-29+2 is used to calculate a preference score (PROPr) by the addition of two Cognitive Function Ability items. Preference-based scores provide an overall summary of health-related quality of life on a common metric. Preference-based scores summarize multiple domains on a metric ranging from 0 (as bad as dead) to 1 (perfect or ideal health).

Time frame:
Baseline, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)
Reported as:
Mean · score on a scale
Change in Quality of Life, as Measured by the PROMIS-29+2
score on a scaleStructured PacingUsual Care
Baseline to MOI0.03 ± 0.110.00 ± 0.10
Baseline to EOI0.06 ± 0.14-0.01 ± 0.11
Baseline to EOS0.06 ± 0.140.01 ± 0.12
SecondaryChange in Quality of Life, as Measured by the EQ-5D 5L

The EQ-5D is a standardized measure of health status. Mobility was measured on a scale from 1 (no problems in walking) to 5 (unable to walk).

Time frame:
Baseline, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)
Reported as:
Mean · score on a scale
Change in Quality of Life, as Measured by the EQ-5D 5L
score on a scaleStructured PacingUsual Care
Baseline to MOI-0.03 ± 0.830.09 ± 0.73
Baseline to EOI-0.06 ± 0.870.13 ± 0.75
Baseline to EOS0.04 ± 0.910.05 ± 0.72
SecondaryChange in Step Count (Physical Activity) as Measured by Actigraphy

Actigraphy will be measured by Fitbit. Participant steps were considered valid from days where they wore the Fitbit at least 10 waking hours. Average steps were calculated from subjects with at least 5 consecutive days of valid data within a week window of their expected visit dates.

Time frame:
Baseline, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)
Reported as:
Mean · steps per day
Change in Step Count (Physical Activity) as Measured by Actigraphy
steps per dayStructured PacingUsual Care
Baseline to MOI116.8 ± 1563.798.03 ± 1784.12
Baseline to EOI305.17 ± 2319.0775.42 ± 1810.99
Baseline to EOS148.40 ± 2256.0-168.64 ± 1725.16
SecondaryChange in Physical Activity, as Measured by the PROMIS SF-Physical Function (PROMIS-PF)

The PROMIS Short Form v2.0 - Physical Function 8b (PROMIS-PF) consists of 8 items. The PROMIS Physical Function instruments measure self-reported capability rather than actual performance of physical activities. T-Scores in a healthy reference population have mean = 50 and standard deviation = 10, with higher scores indicating higher functioning.

Time frame:
Baseline, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)
Reported as:
Mean · T-score
Change in Physical Activity, as Measured by the PROMIS SF-Physical Function (PROMIS-PF)
T-scoreStructured PacingUsual Care
Baseline to MOI-0.13 ± 3.390.14 ± 3.13
Baseline to EOI1.17 ± 4.190.31 ± 3.36
Baseline to EOS1.35 ± 4.620.28 ± 3.72
SecondaryChange in Orthostatic Hypotension, as Measured by the Modified Orthostatic Hypotension Questionnaire (mOHQ)

The Orthostatic Hypotension Questionnaire (OHQ) is a measure of orthostatic intolerance. The modified OHQ (mOHQ) measure used in this study includes a total of ten items related to daily activities and symptoms. The OHQ composite score ranges from 0 (no burden) to 10 (maximal burden). Higher scores are worse. The OHQ composite score includes 6 symptom items (OISA) and 4 daily activity items (OIDAS).

Time frame:
Screening, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)
Reported as:
Mean · score on a scale
Change in Orthostatic Hypotension, as Measured by the Modified Orthostatic Hypotension Questionnaire (mOHQ)
score on a scaleStructured PacingUsual Care
Baseline to MOI-0.91 ± 1.89-0.72 ± 1.63
Baseline to EOI-1.32 ± 2.24-0.63 ± 1.70
Baseline to EOS-1.26 ± 2.34-0.84 ± 1.81
Other pre-specifiedChange in PASC Symptoms, as Measured by the PASC Symptom Questionnaire

The PASC Symptom Questionnaire is a 33-question survey for self-reporting multiple PASC-related symptoms across multiple systems.

Time frame:
Baseline, week 6 (Middle of Intervention), week 12 (EOI), month 6 (EOS)

Results for this outcome have not been posted.

Adverse events

Collected over From first invasive procedure (after consent but before randomization) until end of study, approximately 6 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Structured Pacing0/149 (0%)6/149 (4%)0/149 (0%)
Usual Care0/149 (0%)4/149 (2.7%)0/149 (0%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventStructured PacingUsual Care
Thrombotic thrombocytopenic purpuraBlood and lymphatic system disorders1/1490/149
Atrial fibrillationCardiac disorders1/1490/149
Coronary artery stenosisCardiac disorders1/1490/149
Coeliac artery stenosisGastrointestinal disorders0/1491/149
ConstipationGastrointestinal disorders0/1491/149
Catheter site haemorrhageGeneral disorders0/1491/149
Cholecystitis acuteHepatobiliary disorders0/1491/149
Abdominal wall abscessInfections and infestations0/1491/149
CellulitisInfections and infestations0/1491/149
Pneumonia influenzalInfections and infestations1/1490/149

Baseline characteristics

All randomized subjects who received any randomly assigned treatment. Two subjects in the Structured Pacing group did not receive treatment.

Age, Continuous
Age, Continuous(years)Structured PacingUsual CareTotal
Median50.4 (42.4 to 59.1)50.1 (39.2 to 59.5)50.4 (40.0 to 59.2)
Sex: Female, Male
Sex: Female, Male(Participants)Structured PacingUsual CareTotal
Female113110223
Male363975
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Structured PacingUsual CareTotal
American Indian or Alaska Native101
Asian235
Native Hawaiian or Other Pacific Islander101
Black or African American14923
Middle Eastern or North African101
White125126251
More than one race549
Unknown or Not Reported077
Region of Enrollment
Region of Enrollment(Participants)Structured PacingUsual CareTotal
United States149149298
08

Study locations

1 site
  • All sites listed under NCT06404047
    Durham, North Carolina 27710, United States
09

References and documents

Publications

  • Friedly J, Bateman L, Berdan LG, Casaburi R, Erdmann N, Felker GM, Itchon-Ramos N, Keteyian SJ, MacIntyre N, O'Brien L, Reist C, Rossiter HB, Silverstein A, Taylor E, Pike Welch H, Yanez ND, Zimmerman KO, Make B. Rationale and Design of RECOVER-ENERGIZE: A Platform Clinical Trial of Interventions for Exercise Intolerance With and Without Post-exertional Malaise in Long COVID. medRxiv [Preprint]. 2026 Jun 3:2026.06.02.26354455. doi: 10.64898/2026.06.02.26354455. PubMed 42282195 ↗

Related links

Study documents

  • Protocol and statistical analysis plan · Apr 9, 2025
  • Informed consent form · Apr 15, 2025

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — The summary of the results will be shared on the study website: https://recovercovid.org/

10

Updates

1 registry update since Sep 25, 2026
Results
Results posted
posted Oct 6, 2026
Also revised
primary outcomes
Show all 1 update
  1. Oct 6, 2026
    Results posted
    Primary outcomes Revised (6 changes)
    + 3 other changes: verification date, secondary outcomes and documents

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

11

Registry details

Key details

Study ID
NCT06404073
Lead sponsor
Duke University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Responsible party
Sponsor
First posted
May 8, 2024
Start date
Jul 17, 2024
Primary completion
Aug 18, 2025
Completion
Nov 17, 2025
Results posted
Oct 6, 2026
Last update
Oct 6, 2026

Study contacts

Gary M Felker, MD
study chair · Duke Clinical Research Institute
Barry Make, MD
study chair · National Jewish Health
Lucinda Bateman, MD
study chair · Bateman Horne Center
Janna Friedly, MD, MPH
study chair · University of Washington

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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