Postural Orthostatic Tachycardia SyndromePhase 4NCT05363514
Low Dose Naltrexone Use in Patients With POTS
A Phase 4 study testing Low Dose Naltrexone and Microcrystalline cellulose in people with Postural Orthostatic Tachycardia Syndrome, run by University of Calgary.
Trial summary
Many patients with Postural Orthostatic Tachycardia Syndrome (POTS) experience debilitating fatigue and this significantly impacts their daily lives. Unfortunately, there are no treatments to help POTS patients with their fatigue. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Postural Orthostatic Tachycardia Syndrome
- What is being tested?
- Low Dose Naltrexone and Microcrystalline cellulose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- No sites listed yet
- Study dates
- Jul 2026to Dec 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Physician diagnosis of POTS as defined by the American Autonomic Society consensus statement
- Ability to attend research lab in Calgary, Vancouver or Hamilton, Canada
- Not pregnant and not planning to become pregnant for the duration of the study
- Maintain current other medications at regular doses for the duration of the study
Who cannot join
- Overt cause for postural tachycardia (e.g. acute dehydration, hyperthyroidism)
- Positive pregnancy test
- Breastfeeding
- Other factors which in the investigator's opinion would prevent participant from completing the protocol, including poor compliance during previous studies
- Current use of Low Dose Naltrexone
- Use of opioid containing medications or positive urine opioid test
- History of alcohol, opioid or other substance use disorder
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Rasha Hamzeh, RN contact
About this study
Official title: A Pilot Study of Low Dose Naltrexone Use in Patients With Postural Orthostatic Tachycardia Syndrome
Many patients with Postural Orthostatic Tachycardia Syndrome (POTS) experience debilitating fatigue and this significantly impacts their daily lives. Unfortunately, there are no treatments to help POTS patients with their fatigue. One medication, called low dose naltrexone (LDN), has been tested as a treatment for fatigue in other medical conditions. In this other research, LDN helped patients feel less fatigue. Other research studies have shown that LDN can help reduce markers of inflammation called cytokines. Reducing these cytokines could help reduce symptoms as well. There have been no research studies testing LDN in POTS to date. We are planning to do a research study to test LDN as a treatment to see if it helps POTS patients feel less fatigue.
Read the detailed description
Research Objectives: To evaluate LDN as a treatment for fatigue in patients diagnosed with POTS. The primary hypothesis is that LDN will reduce fatigue in patients with POTS when compared to placebo using a 0-100 Fatigue Visual Analogue Scale. The secondary hypotheses are that LDN will improve quality of life in patients with POTS when compared to placebo using the RAND36 Health Related Quality of Life Survey, and that LDN will reduce inflammatory cytokine concentrations in patients with POTS compared to placebo. Tertiary outcomes will compare autonomic symptoms and orthostatic vital signs between LDN and placebo and also evaluate feasibility of a larger scale clinical trial.
Study Design and Methodology: We will recruit 80 patients with POTS across three sites.Participants will be randomized to the LDN group or the placebo group, for a 16 week study. Before beginning the study drug, POTS patients will complete a baseline assessment including fatigue evaluation, cytokine levels, orthostatic vital signs, orthostatic symptoms, and quality of life. After the baseline assessment, POTS patients will begin the study drug titration (LDN or placebo) as follows: 1.5mg for 2 weeks, 3.0mg for 2 weeks, 4.5 mg for 12 weeks. If participants do not tolerate the target dose (4.5mg), then will reduce to the highest tolerable dose. Participants will complete virtual assessments at 1, 2 and 3 months (surveys). Participants will also be provided with a diary to record symptoms. After 4 months, participants will again attend the research clinic/lab for a final assessment (same procedure as the baseline assessment).
Anticipated Outcomes: These data will allow us to evaluate the efficacy of LDN as a treatment in POTS. The results of this study could be used to inform the feasibility and design of larger clinical trials evaluating LDN use in POTS with funding from a national granting agency.
- Being tested
- Low Dose Naltrexone, Microcrystalline cellulose
- Keywords
- POTS, LDN, Low Dose Naltrexone
- Medical subject headings
- Postural Orthostatic Tachycardia Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose NaltrexoneDrug
Also called LDN
Participant takes Low Dose Naltrexone 4.5mg PO OD for 120 days. Participant will complete a a 4 week titration to target dose of 4.5mg. Week 1-2: 1.5mg PO OD. Week 3-4: 3.0mg PO OD. Week 5-16: 4.5mg PO OD. Participant will be provided with masked capsules in blister packs.
Microcrystalline celluloseDrug
Also called Placebo
Participant takes microcrystalline cellulose 4.5mg PO OD for 120 days. Participant will complete a a 4 week titration to target dose of 4.5mg. Week 1-2: 1.5mg PO OD. Week 3-4: 3.0mg PO OD. Week 5-16: 4.5mg PO OD. Participant will be provided with masked capsules in blister packs.
| Study group | Role | What they receive |
|---|---|---|
| Low Dose Naltrexone | Experimental | Low Dose Naltrexone 4.5mg OD PO. Capsules are masked and provided in blister packs. Receives: Drug: Low Dose Naltrexone |
| Placebo | Placebo comparator | Microcrystalline cellulose 4.5mg OD PO. Capsules are masked and provided in blister packs. Receives: Drug: Microcrystalline cellulose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatigue Visual Analogue Scale (VAS)
Change in Fatigue VAS from pre-treatment (baseline) to treatment (4 months). The score is measured from 0-100 (0 is no fatigue).
Measured: 4 months
Secondary outcomes (2)
RAND 36 Health Related Quality of Life Score
Change in RAND 36 Health Related Quality of Life Score from pre-treatment baseline to treatment (4 months).
Measured: 4 months
Cytokines
Change in plasma cytokine levels from pre-treatment baseline to treatment (4 months)
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2022
- Study startJul 2026 (estimated)
- Primary completionJun 2029 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postural Orthostatic Tachycardia SyndromeStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Satish R Raj, MD MSCI, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05363514
- Sponsor's protocol ID
- REB22-0565
- Status last verified
- Apr 2026
- First submitted
- 2 May 2022
- Last updated
- 1 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Low Dose Naltrexone Use in Patients With Postural Orthostatic Tachycardia Syndrome
- ClinicalTrials.gov ID
- NCT05363514
- Acronym / sponsor ID
- REB22-0565
- Keywords
- POTS, LDN, Low Dose Naltrexone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- Jul 2026 (estimated)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 6 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Many patients with Postural Orthostatic Tachycardia Syndrome (POTS) experience debilitating fatigue and this significantly impacts their daily lives. Unfortunately, there are no treatments to help POTS patients with their fatigue. One medication, called low dose naltrexone (LDN), has been tested as a treatment for fatigue in other medical conditions. In this other research, LDN helped patients feel less fatigue. Other research studies have shown that LDN can help reduce markers of inflammation called cytokines. Reducing these cytokines could help reduce symptoms as well. There have been no research studies testing LDN in POTS to date. We are planning to do a research study to test LDN as a treatment to see if it helps POTS patients feel less fatigue.
Detailed description
Research Objectives: To evaluate LDN as a treatment for fatigue in patients diagnosed with POTS. The primary hypothesis is that LDN will reduce fatigue in patients with POTS when compared to placebo using a 0-100 Fatigue Visual Analogue Scale. The secondary hypotheses are that LDN will improve quality of life in patients with POTS when compared to placebo using the RAND36 Health Related Quality of Life Survey, and that LDN will reduce inflammatory cytokine concentrations in patients with POTS compared to placebo. Tertiary outcomes will compare autonomic symptoms and orthostatic vital signs between LDN and placebo and also evaluate feasibility of a larger scale clinical trial.
Study Design and Methodology: We will recruit 80 patients with POTS across three sites.Participants will be randomized to the LDN group or the placebo group, for a 16 week study. Before beginning the study drug, POTS patients will complete a baseline assessment including fatigue evaluation, cytokine levels, orthostatic vital signs, orthostatic symptoms, and quality of life. After the baseline assessment, POTS patients will begin the study drug titration (LDN or placebo) as follows: 1.5mg for 2 weeks, 3.0mg for 2 weeks, 4.5 mg for 12 weeks. If participants do not tolerate the target dose (4.5mg), then will reduce to the highest tolerable dose. Participants will complete virtual assessments at 1, 2 and 3 months (surveys). Participants will also be provided with a diary to record symptoms. After 4 months, participants will again attend the research clinic/lab for a final assessment (same procedure as the baseline assessment).
Anticipated Outcomes: These data will allow us to evaluate the efficacy of LDN as a treatment in POTS. The results of this study could be used to inform the feasibility and design of larger clinical trials evaluating LDN use in POTS with funding from a national granting agency.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low Dose Naltrexone | Experimental | Drug: Low Dose NaltrexoneLow Dose Naltrexone 4.5mg OD PO. Capsules are masked and provided in blister packs. |
| Placebo | Placebo comparator | Drug: Microcrystalline celluloseMicrocrystalline cellulose 4.5mg OD PO. Capsules are masked and provided in blister packs. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Physician diagnosis of POTS as defined by the American Autonomic Society consensus statement
- Ability to attend research lab in Calgary, Vancouver or Hamilton, Canada
- Not pregnant and not planning to become pregnant for the duration of the study
- Maintain current other medications at regular doses for the duration of the study
Key exclusion criteria (7 listed)
- Overt cause for postural tachycardia (e.g. acute dehydration, hyperthyroidism)
- Positive pregnancy test
- Breastfeeding
- Other factors which in the investigator's opinion would prevent participant from completing the protocol, including poor compliance during previous studies
- Current use of Low Dose Naltrexone
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low Dose NaltrexoneAlso: LDNParticipant takes Low Dose Naltrexone 4.5mg PO OD for 120 days. Participant will complete a a 4 week titration to target dose of 4.5mg. Week 1-2: 1.5mg PO OD. Week 3-4: 3.0mg PO OD. Week 5-16: 4.5mg PO OD. Participant will be provided with masked capsules in blister packs. | Drug | Low Dose Naltrexone |
| Microcrystalline celluloseAlso: PlaceboParticipant takes microcrystalline cellulose 4.5mg PO OD for 120 days. Participant will complete a a 4 week titration to target dose of 4.5mg. Week 1-2: 1.5mg PO OD. Week 3-4: 3.0mg PO OD. Week 5-16: 4.5mg PO OD. Participant will be provided with masked capsules in blister packs. | Drug | Placebo |
Primary outcome
Fatigue Visual Analogue Scale (VAS)
Time frame: 4 months
Change in Fatigue VAS from pre-treatment (baseline) to treatment (4 months). The score is measured from 0-100 (0 is no fatigue).
2 secondary outcomes
RAND 36 Health Related Quality of Life Score
Time frame: 4 months
Cytokines
Time frame: 4 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- Individual participant dataSharing planned: No
Related trials for Postural Orthostatic Tachycardia Syndrome
Recruiting
Ultrasound Guided Stellate Ganglion Block in Postural Tachycardia Syndrome
Postural Tachycardia Syndrome
Enrolling by invitationObservational study
Presentation of Young Adults With and Without Joint Hypermobility
Hypermobile Ehlers-Danlos Syndrome, Postural Orthostatic Tachycardia Syndrome (POTS)
Active, not recruiting
Acute Salt Handling in Orthostatic Intolerance
Postural Tachycardia Syndrome, Orthostatic Tachycardia
Active, not recruitingObservational study
POTS NET mRNA Functional Correlation With NET Activity
Postural Tachycardia Syndrome
Active, not recruiting
Intravenous (IV) Saline and Exercise in Postural Tachycardia Syndrome (POTS)
Postural Tachycardia Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rasha Hamzeh, RN contact
Satish R Raj, MD MSCI principal investigator
University of Calgary
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Low Dose Naltrexone and Microcrystalline cellulose in people with Postural Orthostatic Tachycardia Syndrome, run by University of Calgary.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Satish R Raj, MD MSCI (4032106152, autonomic.research@ucalgary.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fatigue Visual Analogue Scale (VAS) (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2026.