Evaluating the Neuromodulatory Effect of Ketamine in Long COVID-19

NCT06821087 | Enrolling By Invitation Phase 2

• 1 other identifier: STUDY00006367
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Plain Language Summary: This study is a clinical trial to see if ketamine can help treat symptoms of Long COVID, especially fatigue and problems with thinking clearly (often called "brain fog"). Long COVID is a condition that affects people even after they have recovered from COVID-19, causing ongoing health issues like tiredness, memory problems, and difficulty concentrating. Right now, there are very few treatments available for these symptoms, and many people are looking for new options to feel better. What is the study trying to find out? Does ketamine help reduce fatigue and improve thinking skills in people with Long COVID? Does ketamine improve overall quality of life and mental health for people with Long COVID? Is ketamine safe and well-tolerated for people with Long COVID? How does ketamine affect the body's biological processes, like inflammation and brain function? How will the study work? The study will include 20 adults between 18 and 65 years old who have Long COVID symptoms like fatigue or brain fog. Participants will first meet with researchers to answer health questions, take surveys about their symptoms, and do tests to check their thinking skills. All participants will also have a brain scan (MRI) and give a blood sample to look at markers of inflammation. Participants will then receive four ketamine treatments over two weeks at a specialized clinic. The ketamine will be given as an injection, with the dose slightly increasing during the treatment period. After six weeks, participants will return for follow-up tests to see if their symptoms have improved. This includes repeating the surveys, thinking tests, MRI and blood test. Why ketamine? Ketamine is a medicine originally used for anesthesia but has also been found to help with depression and other mental health issues. Researchers think it might help with Long COVID symptoms because it can reduce inflammation in the brain and improve how the brain functions. People with Long COVID often have signs of inflammation and changes in brain chemicals, which ketamine might help balance. What are the potential benefits? Participants might experience less fatigue and clearer thinking after ketamine treatment. They could also feel better overall in terms of mood and quality of life. Since ketamine can work quickly, some people may notice improvements shortly after starting the treatment. What are the risks? Ketamine can cause side effects like feeling dizzy, anxious, or having an unusual sense of reality (sometimes called dissociation). It may also cause temporary increases in blood pressure or heart rate. All treatments will be carefully monitored by healthcare professionals to ensure safety. Who can participate? Adults aged 18-65 with Long COVID who have significant fatigue or thinking problems can join. People will not be able to participate if they have certain health conditions like severe heart disease, uncontrolled high blood pressure, or a history of severe mental health disorders. Why is this study important? Long COVID affects millions of people, and many are struggling to find treatments that work. This study is one of the first to explore ketamine as a potential treatment for Long COVID symptoms. If ketamine helps, it could lead to more research and eventually new treatment options for people living with Long COVID.

Conditions

Long COVID

Keywords

Long COVID; Post-COVID Condition; Post-Acute Sequelae of COVID-19; Brain Fog; Fatigue; Ketamine

Outcome Measures

Primary Outcomes (4)

• PROMIS SF v1.0 - Fatigue 8a

  A patient-reported questionnaire measuring the severity and impact of fatigue on daily activities over the past 7 days. Higher scores indicate greater fatigue.

  At enrollment and at the post-treatment assessment visit, 6 weeks following completion of the ketamine treatment.

• PROMIS SF v2.0 Cognitive Function 4a

  A patient-reported tool that measures perceived cognitive abilities, such as memory, concentration, and mental clarity, over the past 7 days. Higher scores reflect better cognitive function.

  At enrollment and at the post-treatment assessment visit, 6 weeks following completion of the ketamine treatment.

• BrainCheck Cognitive Battery

  A computerized series of neuropsychological tests assessing objective cognitive functions, including memory, attention, executive function, processing speed, and response inhibition. Scores are age-normalized.

  At enrollment and at the post-treatment assessment visit, 6 weeks following completion of the ketamine treatment.

• Number of participants with treatment-related adverse events as assessed by standardized interview

  A standardized interview conducted post-treatment to identify and record any physical or psychological side effects experienced by participants during the ketamine therapy.

  Adverse events will be assessed at each of the four ketamine treatment sessions and during the final post-treatment assessment, which occurs six weeks after the last ketamine injection.

Secondary Outcomes (8)

• PROMIS Global 10 v1.2

  Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).

• NASA Task Load Index (NASA-TLX)

  Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).

• Patient Health Questionnaire-9 (PHQ-9)

  Collected before each ketamine treatment session, at baseline, and at the post-treatment assessment (6 weeks post-treatment).

• Generalized Anxiety Disorder-7 (GAD-7)

  Collected before each ketamine treatment session, at baseline, and at the post-treatment assessment (6 weeks post-treatment).

• Depression in Medically Ill 10 Scale (DMI-10)

  Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).

Study Arms (1)

Ketamine Therapy

EXPERIMENTAL

Participants in this arm will receive four intramuscular (IM) ketamine injections over a two-week period. The initial dose will be 0.5 mg/kg during the first session, increasing to 0.65 mg/kg in the second session, and 0.75 mg/kg for the third and fourth sessions. Injections will be administered at least three days apart. All treatments will be conducted under medical supervision at a specialized clinic with standard safety protocols in place. Vital signs will be monitored before, during, and after each session to assess tolerability. Participants will also undergo assessments of fatigue, cognitive function, quality of life, and biomarkers pre- and post-treatment. Participants will receive fMRI imaging pre- and post-treatment.

Drug: Ketamine only

Interventions

Ketamine only DRUG

Participants in this arm will receive four intramuscular (IM) ketamine injections over a two-week period. The initial dose will be 0.5 mg/kg during the first session, increasing to 0.65 mg/kg in the second session, and 0.75 mg/kg for the third and fourth sessions. Injections will be administered at least three days apart.

Ketamine Therapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18-65 years diagnosed with LC and possess a documented history of positive COVID-19 diagnostic testing or a probable infection as determined by a healthcare provider.
• One persistent symptom of fatigue or neurocognitive dysfunction as defined by rating their symptoms as moderate to severe on the screening form.
• English as a primary language OR comprehension of English suitable to understand research staff instructions.
• All participants must be eligible for MRI and will undergo MRI scans pre- and post-treatment

You may not qualify if:

• Contraindications to ketamine therapy:
• Current substance use disorder
• Current mania or psychosis
• Recent myocardial infarction or stroke (within 1 year)
• Unstable cardiovascular disease (including uncontrolled high blood pressure \> 180/110 mmHg)
• Uncontrolled seizure disorder
• Pregnancy
• Recent COVID-19 infection or reinfection within 8 weeks
• Prior receipt of ketamine treatment
• History of treatment resistant depression (TRD) prior to development of LC
• Defined as completing a trial (2 months of treatment at highest tolerated dose) of 3 or more psychotropic medications from at least 2 classes of medications (i.e. SSRIs, SNRIs, antipsychotic medications, or mood stabilizers such as lithium, lamotrigine, Depakote, or oxcarbazepine)
• Psychotropic medications used during treatment of LC will not be counted as medications used for TRD
• Current severe depression or anxiety, and/or active suicidal ideation
• Severe depression and anxiety defined as scoring \> 19 on PHQ-9 screening or \> 14 on GAD-7 screening.
• Active suicidal ideation is defined as answering "yes" to question #9 on the PHQ-9

Sponsors & Collaborators

• University of Texas at Austin: lead
• Roots Behavioral Health: collaborator

Study Sites (1)

UT Health Austin

Austin, Texas, 78712, United States

Location

Related Publications (41)

• Herrera JE, Niehaus WN, Whiteson J, Azola A, Baratta JM, Fleming TK, Kim SY, Naqvi H, Sampsel S, Silver JK, Verduzco-Gutierrez M, Maley J, Herman E, Abramoff B. Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of fatigue in postacute sequelae of SARS-CoV-2 infection (PASC) patients. PM R. 2021 Sep;13(9):1027-1043. doi: 10.1002/pmrj.12684. Epub 2021 Aug 24. No abstract available.

  PMID: 34346558 BACKGROUND

• Cheng AL, Anderson J, Didehbani N, Fine JS, Fleming TK, Karnik R, Longo M, Ng R, Re'em Y, Sampsel S, Shulman J, Silver JK, Twaite J, Verduzco-Gutierrez M, Kurylo M. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM R. 2023 Dec;15(12):1588-1604. doi: 10.1002/pmrj.13085. Epub 2023 Nov 8. No abstract available.

  PMID: 37937672 BACKGROUND

• Blitshteyn S, Whiteson JH, Abramoff B, Azola A, Bartels MN, Bhavaraju-Sanka R, Chung T, Fleming TK, Henning E, Miglis MG, Sampsel S, Silver JK, Tosto J, Verduzco-Gutierrez M, Putrino D. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of autonomic dysfunction in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM R. 2022 Oct;14(10):1270-1291. doi: 10.1002/pmrj.12894. Epub 2022 Oct 8. No abstract available.

  PMID: 36169154 BACKGROUND

• Melamed E, Rydberg L, Ambrose AF, Bhavaraju-Sanka R, Fine JS, Fleming TK, Herman E, Phipps Johnson JL, Kucera JR, Longo M, Niehaus W, Oleson CV, Sampsel S, Silver JK, Smith MM, Verduzco-Gutierrez M. Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of neurologic sequelae in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM R. 2023 May;15(5):640-662. doi: 10.1002/pmrj.12976. Epub 2023 May 9. No abstract available.

  PMID: 36989078 BACKGROUND

• Global COVID-19 Clinical Platform Case Report Form (CRF) for Post COVID condition (Post COVID-19 CRF). Accessed June 11, 2023. https://www.who.int/publications-detail-redirect/global-covid-19-clinical-platform-case-report-form-(crf)-for-post-covid-conditions-(post-covid-19-crf-)

  BACKGROUND

• Valdes Hernandez Mdel C, Armitage PA, Thrippleton MJ, Chappell F, Sandeman E, Munoz Maniega S, Shuler K, Wardlaw JM. Rationale, design and methodology of the image analysis protocol for studies of patients with cerebral small vessel disease and mild stroke. Brain Behav. 2015 Nov 26;5(12):e00415. doi: 10.1002/brb3.415. eCollection 2015 Dec.

  PMID: 26807340 BACKGROUND

• Groppell S, Soto-Ruiz KM, Flores B, Dawkins W, Smith I, Eagleman DM, Katz Y. A Rapid, Mobile Neurocognitive Screening Test to Aid in Identifying Cognitive Impairment and Dementia (BrainCheck): Cohort Study. JMIR Aging. 2019 Mar 21;2(1):e12615. doi: 10.2196/12615.

  PMID: 31518280 BACKGROUND

• Marcantoni WS, Akoumba BS, Wassef M, Mayrand J, Lai H, Richard-Devantoy S, Beauchamp S. A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: January 2009 - January 2019. J Affect Disord. 2020 Dec 1;277:831-841. doi: 10.1016/j.jad.2020.09.007. Epub 2020 Sep 7.

  PMID: 33065824 BACKGROUND

• Nikolin S, Rodgers A, Schwaab A, Bahji A, Zarate C Jr, Vazquez G, Loo C. Ketamine for the treatment of major depression: a systematic review and meta-analysis. EClinicalMedicine. 2023 Aug 3;62:102127. doi: 10.1016/j.eclinm.2023.102127. eCollection 2023 Aug.

  PMID: 37593223 BACKGROUND

• Lenze EJ, Reiersen AM, Zorumski CF, Santosh PJ. Beyond "Psychotropic": Repurposing Psychiatric Drugs for COVID-19, Alzheimer's Disease, and Cancer. J Clin Psychiatry. 2023 Mar 20;84(3):22r14494. doi: 10.4088/JCP.22r14494.

  PMID: 36946597 BACKGROUND

• Walsh Z, Mollaahmetoglu OM, Rootman J, Golsof S, Keeler J, Marsh B, Nutt DJ, Morgan CJA. Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review. BJPsych Open. 2021 Dec 23;8(1):e19. doi: 10.1192/bjo.2021.1061.

  PMID: 35048815 BACKGROUND

• McIntyre RS, Rosenblat JD, Nemeroff CB, Sanacora G, Murrough JW, Berk M, Brietzke E, Dodd S, Gorwood P, Ho R, Iosifescu DV, Lopez Jaramillo C, Kasper S, Kratiuk K, Lee JG, Lee Y, Lui LMW, Mansur RB, Papakostas GI, Subramaniapillai M, Thase M, Vieta E, Young AH, Zarate CA Jr, Stahl S. Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation. Am J Psychiatry. 2021 May 1;178(5):383-399. doi: 10.1176/appi.ajp.2020.20081251. Epub 2021 Mar 17.

  PMID: 33726522 BACKGROUND

• Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, Saxena S, Kirkwood K, Aan Het Rot M, Lapidus KA, Wan LB, Iosifescu D, Charney DS. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Jun;71(6):681-8. doi: 10.1001/jamapsychiatry.2014.62.

  PMID: 24740528 BACKGROUND

• Singh JB, Fedgchin M, Daly EJ, De Boer P, Cooper K, Lim P, Pinter C, Murrough JW, Sanacora G, Shelton RC, Kurian B, Winokur A, Fava M, Manji H, Drevets WC, Van Nueten L. A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression. Am J Psychiatry. 2016 Aug 1;173(8):816-26. doi: 10.1176/appi.ajp.2016.16010037. Epub 2016 Apr 8.

  PMID: 27056608 BACKGROUND

• Sanacora G, Frye MA, McDonald W, Mathew SJ, Turner MS, Schatzberg AF, Summergrad P, Nemeroff CB; American Psychiatric Association (APA) Council of Research Task Force on Novel Biomarkers and Treatments. A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry. 2017 Apr 1;74(4):399-405. doi: 10.1001/jamapsychiatry.2017.0080.

  PMID: 28249076 BACKGROUND

• McAllister-Williams RH, Arango C, Blier P, Demyttenaere K, Falkai P, Gorwood P, Hopwood M, Javed A, Kasper S, Malhi GS, Soares JC, Vieta E, Young AH, Papadopoulos A, Rush AJ. The identification, assessment and management of difficult-to-treat depression: An international consensus statement. J Affect Disord. 2020 Apr 15;267:264-282. doi: 10.1016/j.jad.2020.02.023. Epub 2020 Feb 7.

  PMID: 32217227 BACKGROUND

• Ketamine - StatPearls - NCBI Bookshelf. Accessed March 12, 2024. https://www.ncbi.nlm.nih.gov/books/NBK470357/

  BACKGROUND

• Cervia-Hasler C, Bruningk SC, Hoch T, Fan B, Muzio G, Thompson RC, Ceglarek L, Meledin R, Westermann P, Emmenegger M, Taeschler P, Zurbuchen Y, Pons M, Menges D, Ballouz T, Cervia-Hasler S, Adamo S, Merad M, Charney AW, Puhan M, Brodin P, Nilsson J, Aguzzi A, Raeber ME, Messner CB, Beckmann ND, Borgwardt K, Boyman O. Persistent complement dysregulation with signs of thromboinflammation in active Long Covid. Science. 2024 Jan 19;383(6680):eadg7942. doi: 10.1126/science.adg7942. Epub 2024 Jan 19.

  PMID: 38236961 BACKGROUND

• Klein J, Wood J, Jaycox JR, Dhodapkar RM, Lu P, Gehlhausen JR, Tabachnikova A, Greene K, Tabacof L, Malik AA, Silva Monteiro V, Silva J, Kamath K, Zhang M, Dhal A, Ott IM, Valle G, Pena-Hernandez M, Mao T, Bhattacharjee B, Takahashi T, Lucas C, Song E, McCarthy D, Breyman E, Tosto-Mancuso J, Dai Y, Perotti E, Akduman K, Tzeng TJ, Xu L, Geraghty AC, Monje M, Yildirim I, Shon J, Medzhitov R, Lutchmansingh D, Possick JD, Kaminski N, Omer SB, Krumholz HM, Guan L, Dela Cruz CS, van Dijk D, Ring AM, Putrino D, Iwasaki A. Distinguishing features of long COVID identified through immune profiling. Nature. 2023 Nov;623(7985):139-148. doi: 10.1038/s41586-023-06651-y. Epub 2023 Sep 25.

  PMID: 37748514 BACKGROUND

• Greene C, Connolly R, Brennan D, Laffan A, O'Keeffe E, Zaporojan L, O'Callaghan J, Thomson B, Connolly E, Argue R, Meaney JFM, Martin-Loeches I, Long A, Cheallaigh CN, Conlon N, Doherty CP, Campbell M. Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment. Nat Neurosci. 2024 Mar;27(3):421-432. doi: 10.1038/s41593-024-01576-9. Epub 2024 Feb 22.

  PMID: 38388736 BACKGROUND

• Krystal JH, Kavalali ET, Monteggia LM. Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacology. 2024 Jan;49(1):41-50. doi: 10.1038/s41386-023-01629-w. Epub 2023 Jul 24.

  PMID: 37488280 BACKGROUND

• Wong AC, Devason AS, Umana IC, Cox TO, Dohnalova L, Litichevskiy L, Perla J, Lundgren P, Etwebi Z, Izzo LT, Kim J, Tetlak M, Descamps HC, Park SL, Wisser S, McKnight AD, Pardy RD, Kim J, Blank N, Patel S, Thum K, Mason S, Beltra JC, Michieletto MF, Ngiow SF, Miller BM, Liou MJ, Madhu B, Dmitrieva-Posocco O, Huber AS, Hewins P, Petucci C, Chu CP, Baraniecki-Zwil G, Giron LB, Baxter AE, Greenplate AR, Kearns C, Montone K, Litzky LA, Feldman M, Henao-Mejia J, Striepen B, Ramage H, Jurado KA, Wellen KE, O'Doherty U, Abdel-Mohsen M, Landay AL, Keshavarzian A, Henrich TJ, Deeks SG, Peluso MJ, Meyer NJ, Wherry EJ, Abramoff BA, Cherry S, Thaiss CA, Levy M. Serotonin reduction in post-acute sequelae of viral infection. Cell. 2023 Oct 26;186(22):4851-4867.e20. doi: 10.1016/j.cell.2023.09.013. Epub 2023 Oct 16.

  PMID: 37848036 BACKGROUND

• Leng A, Shah M, Ahmad SA, Premraj L, Wildi K, Li Bassi G, Pardo CA, Choi A, Cho SM. Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics. Cells. 2023 Mar 6;12(5):816. doi: 10.3390/cells12050816.

  PMID: 36899952 BACKGROUND

• Cysique LA, Jakabek D, Bracken SG, Allen-Davidian Y, Heng B, Chow S, Dehhaghi M, Staats Pires A, Darley DR, Byrne A, Phetsouphanh C, Kelleher A, Dore GJ, Matthews GV, Guillemin GJ, Brew BJ. The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC. Ann Clin Transl Neurol. 2023 Aug;10(8):1338-1352. doi: 10.1002/acn3.51825. Epub 2023 Jun 15.

  PMID: 37318955 BACKGROUND

• Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023 Mar;21(3):133-146. doi: 10.1038/s41579-022-00846-2. Epub 2023 Jan 13.

  PMID: 36639608 BACKGROUND

• Davis HE, Assaf GS, McCorkell L, Wei H, Low RJ, Re'em Y, Redfield S, Austin JP, Akrami A. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021 Aug;38:101019. doi: 10.1016/j.eclinm.2021.101019. Epub 2021 Jul 15.

  PMID: 34308300 BACKGROUND

• Thaweethai T, Jolley SE, Karlson EW, Levitan EB, Levy B, McComsey GA, McCorkell L, Nadkarni GN, Parthasarathy S, Singh U, Walker TA, Selvaggi CA, Shinnick DJ, Schulte CCM, Atchley-Challenner R, Alba GA, Alicic R, Altman N, Anglin K, Argueta U, Ashktorab H, Baslet G, Bassett IV, Bateman L, Bedi B, Bhattacharyya S, Bind MA, Blomkalns AL, Bonilla H, Brim H, Bush PA, Castro M, Chan J, Charney AW, Chen P, Chibnik LB, Chu HY, Clifton RG, Costantine MM, Cribbs SK, Davila Nieves SI, Deeks SG, Duven A, Emery IF, Erdmann N, Erlandson KM, Ernst KC, Farah-Abraham R, Farner CE, Feuerriegel EM, Fleurimont J, Fonseca V, Franko N, Gainer V, Gander JC, Gardner EM, Geng LN, Gibson KS, Go M, Goldman JD, Grebe H, Greenway FL, Habli M, Hafner J, Han JE, Hanson KA, Heath J, Hernandez C, Hess R, Hodder SL, Hoffman MK, Hoover SE, Huang B, Hughes BL, Jagannathan P, John J, Jordan MR, Katz SD, Kaufman ES, Kelly JD, Kelly SW, Kemp MM, Kirwan JP, Klein JD, Knox KS, Krishnan JA, Kumar A, Laiyemo AO, Lambert AA, Lanca M, Lee-Iannotti JK, Logarbo BP, Longo MT, Luciano CA, Lutrick K, Maley JH, Mallett G, Marathe JG, Marconi V, Marshall GD, Martin CF, Matusov Y, Mehari A, Mendez-Figueroa H, Mermelstein R, Metz TD, Morse R, Mosier J, Mouchati C, Mullington J, Murphy SN, Neuman RB, Nikolich JZ, Ofotokun I, Ojemakinde E, Palatnik A, Palomares K, Parimon T, Parry S, Patterson JE, Patterson TF, Patzer RE, Peluso MJ, Pemu P, Pettker CM, Plunkett BA, Pogreba-Brown K, Poppas A, Quigley JG, Reddy U, Reece R, Reeder H, Reeves WB, Reiman EM, Rischard F, Rosand J, Rouse DJ, Ruff A, Saade G, Sandoval GJ, Santana JL, Schlater SM, Sciurba FC, Shepherd F, Sherif ZA, Simhan H, Singer NG, Skupski DW, Sowles A, Sparks JA, Sukhera FI, Taylor BS, Teunis L, Thomas RJ, Thorp JM, Thuluvath P, Ticotsky A, Tita AT, Tuttle KR, Urdaneta AE, Valdivieso D, VanWagoner TM, Vasey A, Verduzco-Gutierrez M, Wallace ZS, Ward HD, Warren DE, Weiner SJ, Welch S, Whiteheart SW, Wiley Z, Wisnivesky JP, Yee LM, Zisis S, Horwitz LI, Foulkes AS; RECOVER Consortium. Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection. JAMA. 2023 Jun 13;329(22):1934-1946. doi: 10.1001/jama.2023.8823.

  PMID: 37278994 BACKGROUND

• Perlis RH, Santillana M, Ognyanova K, Safarpour A, Lunz Trujillo K, Simonson MD, Green J, Quintana A, Druckman J, Baum MA, Lazer D. Prevalence and Correlates of Long COVID Symptoms Among US Adults. JAMA Netw Open. 2022 Oct 3;5(10):e2238804. doi: 10.1001/jamanetworkopen.2022.38804.

  PMID: 36301542 BACKGROUND

• Logue JK, Franko NM, McCulloch DJ, McDonald D, Magedson A, Wolf CR, Chu HY. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open. 2021 Feb 1;4(2):e210830. doi: 10.1001/jamanetworkopen.2021.0830.

  PMID: 33606031 BACKGROUND

• Bull-Otterson L, Baca S, Saydah S, et al. Post-COVID Conditions Among Adult COVID-19 Survivors Aged 18-64 and ≥65 Years - United States, March 2020-November 2021. MMWR Morb Mortal Wkly Rep. 2022;71(21):713-717. doi:10.15585/mmwr.mm7121e1

  BACKGROUND

• CDC. Post-COVID Conditions. Centers for Disease Control and Prevention. Published September 1, 2022. Accessed December 6, 2022. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html

  BACKGROUND

• Chakraborty C, Bhattacharya M. The current landscape of long COVID clinical trials: NIH's RECOVER to Stanford Medicine's STOP-PASC initiative. Mol Ther Nucleic Acids. 2023 Aug 28;33:887-889. doi: 10.1016/j.omtn.2023.08.016. eCollection 2023 Sep 12. No abstract available.

  PMID: 37680987 RESULT

• Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol. 1987 Aug;149(2):351-6. doi: 10.2214/ajr.149.2.351.

  PMID: 3496763 RESULT

• Nikolich JZ, Rosen CJ. Toward Comprehensive Care for Long Covid. N Engl J Med. 2023 Jun 8;388(23):2113-2115. doi: 10.1056/NEJMp2304550. Epub 2023 May 9. No abstract available.

  PMID: 37158440 RESULT

• Kopra E, Mondelli V, Pariante C, Nikkheslat N. Ketamine's effect on inflammation and kynurenine pathway in depression: A systematic review. J Psychopharmacol. 2021 Aug;35(8):934-945. doi: 10.1177/02698811211026426. Epub 2021 Jun 26.

  PMID: 34180293 RESULT

• Lullau APM, Haga EMW, Ronold EH, Dwyer GE. Antidepressant mechanisms of ketamine: a review of actions with relevance to treatment-resistance and neuroprogression. Front Neurosci. 2023 Aug 8;17:1223145. doi: 10.3389/fnins.2023.1223145. eCollection 2023.

  PMID: 37614344 RESULT

• Kang MJY, Hawken E, Vazquez GH. The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity. Front Psychiatry. 2022 Apr 25;13:860882. doi: 10.3389/fpsyt.2022.860882. eCollection 2022.

  PMID: 35546951 RESULT

• Meier TB, Savitz J. The Kynurenine Pathway in Traumatic Brain Injury: Implications for Psychiatric Outcomes. Biol Psychiatry. 2022 Mar 1;91(5):449-458. doi: 10.1016/j.biopsych.2021.05.021. Epub 2021 May 31.

  PMID: 34266671 RESULT

• Al-Aly Z, Topol E. Solving the puzzle of Long Covid. Science. 2024 Feb 23;383(6685):830-832. doi: 10.1126/science.adl0867. Epub 2024 Feb 22.

  PMID: 38386747 RESULT

• Aziz R, Siles N, Kelley M, Wylie D, Melamed E, Brode WM. Clinical characteristics of Long COVID patients presenting to a dedicated academic post-COVID-19 clinic in Central Texas. Sci Rep. 2023 Dec 11;13(1):21971. doi: 10.1038/s41598-023-48502-w.

  PMID: 38081885 RESULT

• Xie Y, Bowe B, Al-Aly Z. Burdens of post-acute sequelae of COVID-19 by severity of acute infection, demographics and health status. Nat Commun. 2021 Nov 12;12(1):6571. doi: 10.1038/s41467-021-26513-3.

  PMID: 34772922 RESULT

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Mental Fatigue; Fatigue

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Behavioral Symptoms; Behavior

Study Officials

• W. Michael Brode, MD

  University of Texas at Austin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Internal Medicine

Study Record Dates

• First Submitted: February 10, 2025
• First Posted: February 11, 2025
• Study Start: April 28, 2025
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The de-identified IPD will be made available beginning 6 months after publication of the primary study results. Data will be available for a period of 3 years following this initial release.
• Access Criteria: Data will be shared with qualified researchers affiliated with academic institutions, healthcare organizations, or other research entities conducting studies related to Long COVID, neurocognitive function, or ketamine treatment. Researchers must submit a formal data request, including a summary of the proposed research and intended use of the data. Requests will be reviewed by the study's principal investigator and research team to ensure alignment with ethical guidelines and scientific merit. Approved researchers will be required to sign a data use agreement to ensure proper handling and confidentiality of the data.

Locations

US (1)