Trial Report Low-dose naltrexone and NAD+ for the treatment of patients with persistent fatigue symptoms after COVID-19, 2024, Isman

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https://www.sciencedirect.com/science/article/pii/S2666354624000115

Brain, Behavior, & Immunity - Health
Volume 36, March 2024, 100733

Low-dose naltrexone and NAD+ for the treatment of patients with persistent fatigue symptoms after COVID-19
Anar Isman a, Andy Nyquist a,*, Bailey Strecker a, Girish Harinath a, Virginia Lee a,
Xingyu Zhang b, Sajad Zalzala
a
AgelessRx, 2370 E Stadium Blvd #2049, Ann Arbor, MI, 48104, USA
b
Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, 15213, USA
Received 31 July 2023, Revised 15 December 2023, Accepted 25 January 2024, Available online 1 February 2024, Version of Record 6 February 2024.



https://doi.org/10.1016/j.bbih.2024.100733Get rights and content

open access

Highlights



  • A subset of patients experienced persistent fatigue symptoms after COVID-19.


  • Treatment with low-dose naltrexone (LDN) and NAD+ was well tolerated.


  • Treatment increased SF-36 quality of life scores.


  • Treatment also improved fatigue symptom scores.


  • A subset of patients were clinically responsive.


Abstract

A subset of patients experiences persistent fatigue symptoms after COVID-19, and patients may develop long COVID, which is characterized by lasting systemic symptoms.

No treatments for this condition have been validated and are urgently warranted.

In this pilot study, we assessed whether treatment with low-dose naltrexone (LDN, 4.5 mg/day) and supplementation with NAD + through iontophoresis patches could improve fatigue symptoms and quality of life in 36 patients with persistent moderate/severe fatigue after COVID-19.

We detected a significant increase from baseline in SF-36 survey scores after 12 weeks of treatment (mean total SF-36 score 36.5 [SD: 15.6] vs. 52.1 [24.8]; p < 0.0001), suggestive of improvement of quality of life.

Furthermore, participants scored significantly lower on the Chalder fatigue scale after 12 weeks of treatment (baseline: 25.9 [4.6], 12 weeks: 17.4 [9.7]; p < 0.0001).

We found a subset of 52 % of patients to be responders after 12 weeks of treatment.

Treatment was generally safe, with mild adverse events previously reported for LDN, which could be managed with dose adjustments.

The iontophoresis patches were associated with mild, short-lived skin irritation in 25 % of patients.

Our data suggest treatment with LDN and NAD+ is safe and may be beneficial in a subset of patients with persistent fatigue after COVID-19.

Larger randomized controlled trials will have to confirm our data and determine which patient subpopulations might benefit most from this strategy.


 
Open label, uncontrolled.

Participants were treated for 12 weeks with LDN and NAD +. Participants were actively seeking out treatment for their fatigue symptoms and were found to be largely unwilling to participate in a placebo controlled trial, with the risk of not receiving treatment. This resulted in difficulties in the accrual of enough patients for the trial, and therefore, after July 30, 2021, patients were placed in an unblinded open label observational treatment arm, and we offered participants (N = 3) initially randomized into the control group to enroll in the treatment group.

Subjective outcome reporting.

Validated surveys were completed by participants at baseline, and at 2, 4, 8, and 12 weeks after the start of treatment. The Chalder Fatigue Scale is a widely used self-assessment tool for chronic fatigue, including ME/CFS. This scale was used to assess fatigue symptoms, and the Short Form 36 (SF-36) survey was used to measure various aspects of quality of life. The SF-36 is a validated survey measuring the quality of life of healthy adults or patients. The Chalder Fatigue Scale was assessed using Likert scaling. Furthermore, participants were asked to answer surveys assessing adverse events, and other health-related questions.
 
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