Oral Ketamine for Sickle Cell Pain

Overseen By Kimberly Lobo, MPH

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Boston Children's Hospital

Disqualifiers: Ketamine side effects, patient refusal

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 1

Duration: 2 days

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of oral ketamine (Ketamine Hydrochloride) in managing severe pain during sickle cell crises in children and teens. Typically, these young patients depend on strong painkillers like opioids, which may not always work and can cause side effects. The trial aims to determine if adding oral ketamine can better control pain without relying solely on these heavy-duty drugs. Eligible participants are children and adolescents aged 12 to 24 admitted to the hospital for sickle cell pain. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that oral ketamine is likely to be safe for children and adolescents with sickle cell pain?

Research has shown that ketamine is often used with opioids to manage pain during sickle cell crises, but clear evidence on its safety for this specific use remains limited. Ketamine, in low doses, has been safely used for pain relief in various situations, such as surgeries and pediatric care, indicating it is generally well-tolerated. However, more research is needed to understand its safety and effectiveness specifically for sickle cell pain. The study's later phase suggests that earlier research did not identify major safety concerns. Prospective participants should discuss any questions or concerns with the study team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell pain?

Oral Ketamine is unique because it offers a new approach to managing sickle cell pain. Unlike traditional treatments that often rely on opioids, Oral Ketamine utilizes ketamine hydrochloride, which works by blocking NMDA receptors in the brain. This different mechanism of action can provide pain relief without the typical side effects and risk of addiction associated with opioids. Researchers are excited about its potential to offer faster and more effective pain management for sickle cell patients, addressing a critical need in current treatment options.

What evidence suggests that oral ketamine might be an effective treatment for sickle-cell pain?

Research has shown that ketamine, which participants in this trial may receive, can effectively manage pain during sickle cell crises. Studies have found that ketamine provides pain relief similar to traditional painkillers like opioids, which often cause unpleasant side effects. In both adults and children, ketamine effectively reduces pain. Importantly, ketamine works faster to relieve pain, which is crucial during painful sickle cell episodes. This makes ketamine a promising option for improved pain management in sickle cell disease. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for children and adolescents aged 12-24 who are admitted to the hospital with vaso-occlusive pain due to sickle cell crises. It's not for those who've had bad reactions to IV ketamine before or if they choose not to participate.

Inclusion Criteria

I am between 12 and 24 years old and need hospital care for pain from blocked blood vessels.

Exclusion Criteria

I do not want to participate in the clinical trial.

I've had bad reactions to ketamine IV for pain before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Oral ketamine is administered every 8 hours for 48 hours to treat vaso-occlusive pain in adolescents and young adults

2 days

Continuous monitoring in hospital

Follow-up

Participants discuss with the Pain Service and Hematology Service whether to continue oral ketamine, change to intravenous ketamine, or discontinue ketamine

1 day

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine Hydrochloride

Trial Overview The study tests oral ketamine as a supplement to IV opioids in managing severe pain during sickle-cell crises. Patients will take oral ketamine every 8 hours over two days, with continuous monitoring and evaluations by the Pain Service.

How Is the Trial Designed?

Group I: Ketamine Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Published Research Related to This Trial

A case study of a 31-year-old male with sickle cell disease showed that low-dose ketamine infusion, used alongside opioids, effectively managed pain, with 82.35% of patients reporting reduced pain intensity and decreased opioid use.

Only one out of 17 patients experienced a serious side effect from ketamine, suggesting it is a relatively safe option for pain management in sickle cell disease, although further randomized trials are needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine infusion for sickle cell pain crisis refractory to opioids: a case report and review of literature. Uprety, D., Baber, A., Foy, M.[2022]

In a study involving 240 children with severe sickle cell disease pain, intravenous ketamine (1 mg/kg) was found to be as effective as intravenous morphine (0.1 mg/kg) for pain relief, achieving a maximum reduction in pain scores of 66.4% compared to 61.3%.

While ketamine provided comparable analgesic effects, it was associated with a higher incidence of transient, non-life threatening side effects (37.5% vs. 3.3% for morphine), suggesting it could be a viable alternative for pain management in settings where morphine is less accessible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose ketamine versus morphine for acute severe vaso occlusive pain in children: a randomized controlled trial. Lubega, FA., DeSilva, MS., Munube, D., et al.[2022]

In a study involving 22 pediatric patients with sickle cell disease, subanesthetic ketamine infusion significantly reduced pain scores within 24 hours and decreased opioid requirements, indicating its efficacy in managing pain associated with SCD.

The treatment was generally safe, with only 23.9% of admissions experiencing hallucinations as a side effect, and only 8.7% requiring cessation of the infusion due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for Pain in Sickle Cell Disease Reduces Opioid Usage. Onyebuchi, CO., Chumpitazi, CE., Placencia, JL., et al.[2023]

Oral ketamine has shown effectiveness in managing pain during invasive procedures in children with cancer, indicating its potential as a pain relief option.

A case report highlights that oral ketamine successfully relieved end-stage cancer pain in a pediatric patient who was resistant to opioid treatments, suggesting its efficacy in severe cancer pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral ketamine for pain relief in a child with abdominal malignancy. Ugur, F., Gulcu, N., Boyaci, A.[2013]

Low-dose ketamine infusion (LDKI) was well tolerated in 19 pediatric patients (12 with cancer and 7 with sickle cell disease) over a median treatment duration of 6 days, with no patients discontinuing due to intolerability.

While LDKI did not significantly change pain scores or opioid use during treatment, patients with sickle cell disease experienced a median 32% reduction in cumulative pain scores compared to previous admissions for vaso-occlusive events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose Ketamine Infusion for Pediatric Hematology/Oncology Patients: Case Series and Literature Review. Yu, H., Chen, A., Chen, E., et al.[2023]

A case report of a 35-year-old male with sickle cell disease showed that low-dose ketamine infusion effectively managed severe pain and allowed for opioid weaning after traditional opioid treatments failed.

This case supports the use of low-dose ketamine as a safe and effective nonopioid analgesic for patients with chronic pain conditions, including those with sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine as an Analgesic Adjunct for Opioid-Induced Hyperalgesia in a Patient With a Sickle Cell Pain Episode. Martinez, MR., Garmon, EH., Starling, GD., et al.[2022]

In a study using Chinese hamster lung fibroblast cells, both N-nitrosoketamine (NKT) and ketamine (KT) were found to be genotoxic after short-term exposure, indicating potential DNA damage, while continuous exposure did not show this effect.

NKT exhibited a stronger genotoxic effect compared to KT, suggesting that the recreational use of NKT may pose greater risks for genetic damage than the medically used form of ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotoxic effects of N-nitrosoketamine and ketamine as assessed by in vitro micronucleus test in Chinese hamster lung fibroblast cell line. Toyama, Y., Shimizu, H., Suzuki, Y., et al.[2021]

Oral ketamine at dosages of 0.25-1 mg/kg/dose is considered safe for treating chronic pain in children over a 14-day period, with only mild toxicities observed at higher doses.

Out of 12 children studied, 5 showed improvement in pain scores, with 2 experiencing complete pain resolution lasting more than 4 weeks after stopping treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral ketamine for children with chronic pain: a pilot phase 1 study. Bredlau, AL., McDermott, MP., Adams, HR., et al.[2022]

In a study involving 100 administrations of intravenous ketamine hydrochloride (2 mg/kg) and atropine (0.2 mg) to children, no serious side effects were reported, indicating a strong safety profile for this combination in a pediatric setting.

Ketamine significantly alleviated pain and distress during routine medical procedures, improving the experience for both children and healthcare providers, and reducing the anxiety associated with repeated procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine anaesthesia for medical procedures in children. Elliott, E., Hanid, TK., Arthur, LJ., et al.[2019]

Low-dose ketamine infusions in pediatric patients with sickle cell disease have been found to significantly improve pain scores during painful crises, indicating its efficacy as a pain management option.

The use of ketamine also led to a reduction in opioid usage, suggesting it may help minimize reliance on stronger pain medications in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine Infusion for Pain Control in Acute Pediatric Sickle Cell Painful Crises. Hagedorn, JM., Monico, EC.[2019]

This study evaluates the efficacy and safety of intranasal ketamine as an adjunct to standard pain therapy for children aged 4-16 with sickle cell disease experiencing painful vaso-occlusive crises, aiming to improve pain management in resource-limited settings.

The trial is designed as a multicentered, randomized, double-blind, placebo-controlled study, with primary endpoints focusing on changes in self-reported pain levels and monitoring for adverse events, ensuring a rigorous assessment of ketamine's effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subdissociative intranasal ketamine plus standard pain therapy versus standard pain therapy in the treatment of paediatric sickle cell disease vaso-occlusive crises in resource-limited settings: study protocol for a randomised controlled trial. Young, JR., Sawe, HR., Mfinanga, JA., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7839575/

Ketamine for Sickle Cell Vaso-Occlusive Crises: A Systematic ... Ketamine has a potentially comparable efficacy with other opioids in reducing the pain during VOC in SCD patients.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9292870/

Ketamine administration for acute painful sickle cell crisis The objective was to evaluate the efficacy and safety of single‐dose ketamine infusion in adults with sickle cell disease (SCD) who presented with acute sickle ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03296345

Adjuvant Low-dose Ketamine in Pediatric Sickle Cell Vaso ... Intravenous (IV) ketamine has demonstrated efficacy in reducing post-operative, chronic, and cancer-related pain in pediatrics, as well as in reducing time to ...

4. journals.lww.com journals.lww.com/sjmm/fulltext/2021/09010/ketamine_for_sickle_cell_vaso_occlusive_crises__a.2.aspx

Ketamine for Sickle Cell Vaso-Occlusive Crises Ketamine has a potentially comparable efficacy with other opioids in reducing the pain during VOC in SCD patients.

5. dig.pharmacy.uic.edu dig.pharmacy.uic.edu/faqs/2023-2/july-2023-faqs/what-evidence-supports-the-use-of-ketamine-in-pain-management-of-vaso-occlusive-episodes-in-patients-with-sickle-cell-disease/

What evidence supports the use of ketamine in pain ... What evidence supports the use of ketamine in pain management of vaso-occlusive episodes in patients with sickle cell disease?

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05378555?term=AREA%5BBasicSearch%5D(a%20vaso)&rank=7

Oral Ketamine for Treatment of Vaso-Occlusive Pain The purpose of this study is to learn more about the feasibility of oral ketamine for the treatment of painful sickle-cell crises in children and ...

7. degruyterbrill.com degruyterbrill.com/document/doi/10.1515/sjpain-2017-0140/html?lang=en&srsltid=AfmBOorYIywDc3q1C_pTII7vLv972iIpkINhq6bcsnAyYOYeaaoCSk3v

Low dose ketamine versus morphine for acute severe vaso ... Ketamine is cheap, widely safe, readily available drug, with analgesic effects at sub-anesthetic doses and has been used in wide range of surgeries, pediatric ...