IV Saline for POTS and Long COVID

Overseen By Rasha Hamzeh, RN

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Disqualifiers: Dehydration, Bed rest, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 3 hours

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial may require you to stop taking certain medications if they could interfere with the test results, but it doesn't specify which ones. It's best to discuss your current medications with the trial team to see if any changes are needed.

Is IV saline generally safe for humans?

The research articles provided do not contain relevant safety information about IV saline for humans. ^{1 2 3 4 5}

How does the IV saline treatment for POTS and Long COVID differ from other treatments?

IV saline treatment is unique because it involves administering a large volume (999 mL) of normal saline directly into the bloodstream, which can help improve blood volume and circulation. This approach is different from oral medications or lifestyle changes typically used for POTS and Long COVID, as it provides immediate hydration and electrolyte balance. ^{6 7 8 9 10}

What is the purpose of this trial?

Patients with Postural Orthostatic Tachycardia Syndrome (POTS) and Post-Acute Sequelae of COVID (PASC, or "Long COVID") experience cognitive dysfunction. The investigators will test the hypothesis that 999 mL of IV saline will improve cognitive function in patients with POTS and Long COVID compared to placebo (50 mL of saline).

Research Team

Satish R Raj, MD MSCI

Principal Investigator

University of Calgary

Eligibility Criteria

This trial is for adults aged 18-60 with Long COVID or Postural Orthostatic Tachycardia Syndrome (POTS) who experience 'brain fog' or cognitive issues. Healthy individuals without POTS or brain fog can also participate. People must have had a positive SARS-CoV-2 test and symptoms persisting over 12 weeks.

Inclusion Criteria

I am either male or female.

I have been diagnosed with Long COVID.

SARS-COV2 test positive

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 999 mL or 50 mL of normal saline intravenously, followed by cognitive and physiological testing

3 hours

2 visits (in-person)

Follow-up

Participants complete a series of validated questionnaires to assess psychiatric symptoms

1 week

Online survey

Treatment Details

Interventions

• IV normal saline (50 mL infusion)
• IV normal saline (999 mL infusion)

Trial Overview The study tests if giving patients with POTS and Long COVID a large volume of IV saline (999 mL) improves their cognitive function compared to a much smaller dose (50 mL, considered as placebo).

Participant Groups

Group I: 999 mL normal Saline Experimental Treatment 1 Intervention

999 mL of normal saline infused intravenously.

Group II: 50 mL normal Saline Placebo Group 1 Intervention

50 mL of normal saline infused intravenously.

IV normal saline (999 mL infusion) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Normal Saline for:

• Dehydration
• Hypovolemia
• Shock
• Metabolic acidosis
• Hyponatremia
• Hypernatremia
• Fluid replacement
• Electrolyte disturbances

Approved in European Union as Sodium Chloride for:

• Dehydration
• Hypovolemia
• Shock
• Metabolic acidosis
• Hyponatremia
• Hypernatremia
• Fluid replacement
• Electrolyte disturbances

Approved in Canada as Normal Saline for:

• Dehydration
• Hypovolemia
• Shock
• Metabolic acidosis
• Hyponatremia
• Hypernatremia
• Fluid replacement
• Electrolyte disturbances

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Findings from Research

A new liquid suppository system using sodium chloride and poloxamers was developed for diclofenac sodium, which was easier to administer and showed no leakage after insertion, unlike previous formulations with bioadhesive polymers that caused drug precipitation.

The liquid suppository demonstrated significantly higher initial plasma concentrations and faster absorption of diclofenac sodium compared to solid suppositories, indicating it is a more effective and convenient rectal dosage form.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physicochemical characterization and in vivo evaluation of thermosensitive diclofenac liquid suppository. Yong, CS., Choi, YK., Kim, YI., et al.[2019]

The thermosensitive poloxamer gel loaded with diclofenac sodium showed faster absorption and higher initial plasma concentrations in rats compared to traditional semi-solid suppositories, indicating improved efficacy for rectal delivery.

The formulation was safe, as it did not cause any morphological damage to rectal tissues, suggesting that poloxamer gels with sodium chloride could be a safer alternative for delivering diclofenac sodium rectally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of sodium chloride on the release, absorption and safety of diclofenac sodium delivered by poloxamer gel. Park, YJ., Yong, CS., Kim, HM., et al.[2019]

In a study involving 42 healthy adults, intravenous diclofenac sodium (DFP-08) at doses of 18.75 mg and 37.5 mg showed similar exposure levels to a 50 mg oral diclofenac potassium tablet, indicating effective absorption and dose proportionality.

The intravenous formulation was well tolerated over 7 days, with only mild adverse events reported, suggesting a favorable safety profile, although further studies are needed to fully assess its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects. Munjal, S., Gautam, A., Okumu, F., et al.[2016]

In a study of 10 ICU patients, intravenous diclofenac sodium at a dose of 0.2 mg/kg effectively reduced fever, with 9 out of 10 patients experiencing a temperature drop of over 0.5 degrees C within 1 hour.

The treatment was well-tolerated, showing no major side effects, and any transient changes in renal function did not require further intervention, indicating its safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antipyretic therapy in ICU patients: evaluation of low dose diclofenac sodium. Pesenti, A., Riboni, A., Basilico, E., et al.[2019]

In a study involving 12 patients with acute cerebral damage, continuous low-dose infusion of diclofenac sodium successfully achieved normothermia (temperature < 37.5°C) without major side effects, indicating its efficacy as an antipyretic.

The treatment also led to a significant reduction in intracranial pressure while maintaining stable mean arterial pressure, suggesting improved cerebral perfusion without negatively impacting renal or liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Control of fever by continuous, low-dose diclofenac sodium infusion in acute cerebral damage patients. Cormio, M., Citerio, G., Spear, S., et al.[2019]

In a study involving 50 pediatric patients aged 6 to 18 years, 72% reported taste and odor disturbances after flushing IV lines with prefilled syringes of normal saline, compared to only 4% with freshly prepared saline, indicating a significant difference (p < 0.001).

The findings suggest that the plastic materials in commercially available prefilled syringes may leach volatile substances into the saline, causing these disturbances, highlighting the importance of preparation methods in minimizing patient discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taste and Odour Disturbances in Pediatric Patients Undergoing IV Flush with Normal Saline Administered by Prefilled or Freshly Prepared Syringes: Randomized Single-Blind Study. Mancini, D., Vaillancourt, R., Pouliot, A., et al.[2019]

In a study of 83 patients over 5 years, normal saline instillation during negative pressure wound therapy showed comparable outcomes to an antiseptic solution (0.1% polyhexanide plus 0.1% betaine) in terms of wound dehiscence, recurrence, and re-operations, with no significant differences between the two groups.

The findings suggest that normal saline is an effective and accessible option for treating infected wounds, potentially allowing for broader use in clinical settings due to its cost-effectiveness and similar efficacy to antiseptic solutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcome Assessment Between Antiseptic and Normal Saline for Negative Pressure Wound Therapy with Instillation. Meshkin, DH., Fan, KL., Charipova, K., et al.[2021]

This multicenter trial aims to compare the effects of balanced crystalloids versus normal saline on plasma chloride concentration in patients with predicted severe acute pancreatitis, with a primary endpoint of measuring chloride levels on day 3 after enrollment.

The study will also assess secondary outcomes related to kidney health and overall clinical status, providing valuable data to inform future research on fluid therapy in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Normal Saline or Balanced Crystalloid on Plasma Chloride Concentration and Acute Kidney Injury in Patients With Predicted Severe Acute Pancreatitis: Protocol of a Phase II, Multicenter, Stepped-Wedge, Cluster-Randomized, Controlled Trial. Ye, B., Huang, M., Chen, T., et al.[2021]

In a study of 47 adults with severe burns (over 20% of total body surface area), hypertonic saline was found to be a safe and effective resuscitation fluid, allowing for less fluid delivery while achieving adequate urinary output.

Patients receiving hypertonic saline plus colloid (like albumin) showed improved resuscitation outcomes, and none experienced changes in pH or renal function, indicating that this method can be beneficial in managing burn injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypertonic saline resuscitation: efficacy in a community-based burn unit. Griswold, JA., Anglin, BL., Love, RT., et al.[2013]

In a study of very preterm infants (23 to 31 weeks gestational age), those who received early saline boluses showed a higher rate of death or disability (53.6%) compared to those who did not receive saline (32.1%).

Infants receiving saline boluses also had significantly worse long-term neurodevelopmental outcomes, including higher rates of cerebral palsy and lower scores in motor and language development, suggesting potential risks associated with this common resuscitation practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of saline boluses in very preterm infants. Aslam, A., Vincer, M., Allen, A., et al.[2019]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Physicochemical characterization and in vivo evaluation of thermosensitive diclofenac liquid suppository. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of sodium chloride on the release, absorption and safety of diclofenac sodium delivered by poloxamer gel. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Antipyretic therapy in ICU patients: evaluation of low dose diclofenac sodium. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Control of fever by continuous, low-dose diclofenac sodium infusion in acute cerebral damage patients. [2019]

6. Canada pubmed.ncbi.nlm.nih.gov

Taste and Odour Disturbances in Pediatric Patients Undergoing IV Flush with Normal Saline Administered by Prefilled or Freshly Prepared Syringes: Randomized Single-Blind Study. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Long-Term Outcome Assessment Between Antiseptic and Normal Saline for Negative Pressure Wound Therapy with Instillation. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

The Impact of Normal Saline or Balanced Crystalloid on Plasma Chloride Concentration and Acute Kidney Injury in Patients With Predicted Severe Acute Pancreatitis: Protocol of a Phase II, Multicenter, Stepped-Wedge, Cluster-Randomized, Controlled Trial. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Hypertonic saline resuscitation: efficacy in a community-based burn unit. [2013]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term outcomes of saline boluses in very preterm infants. [2019]