Hereditary Spastic ParaplegiaPhase 4NCT07542548
D-Cycloserine for Serine Palmitoyltransferase Inhibition
A Phase 4 study testing D-cycloserine in people with Hereditary Spastic Paraplegia, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The overarching objective of this study is to mitigate the neurological decline associated with SPTSSA related Complex Hereditary Spastic Paraplegia Read more about this study
- Who is it for?
- Ages 6 to 6 years, women only
- Conditions the study is for
- Hereditary Spastic Paraplegia
- What is being tested?
- D-cycloserine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jul 2024to 17 Mar 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 6 to 6 years
- Women only
- No healthy volunteers
- Child
Who may be able to join
- • Informed consent provided by the participant's parents.
- Ability to travel to the study and assessment sites (Massachusetts General Hospital Main Campus, 55 Fruit St, Boston, MA 02114 and MGH IHP Impact Practice Center, 2 Constitution Wharf, Charlestown, MA 02129) and adhere to study-related follow-up examinations and/or procedures and provide access to participant's medical records.
- Clinical phenotype, neuroimaging, genetic testing and biochemical results consistent with a diagnosis of SPTSSA-related Complex Hereditary Spastic Paraplegia
Who cannot join
- • Participant has any known contraindication to or unwillingness to undergo procedures listed in the protocol
- Use of investigational medication within 5 half-lives of the drug at enrollment
- Participant has any condition that, in the opinion of the Site Investigator, would ultimately prevent the completion of study procedures.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: D-Cycloserine for Serine Palmitoyltransferase Inhibition: Treatment of a Single Patient With a Complex Hereditary Spastic Paraplegia Due to a De Novo Variant in the SPTSSA Gene
The overarching objective of this study is to mitigate the neurological decline associated with SPTSSA related Complex Hereditary Spastic Paraplegia
Read the detailed description
At each visit a medication reconciliation will be performed which will include medications, vitamins, herbal preparations, and supplements. For each medication the investigators will record start and end dates of administration, dosage, frequency, and reason for use. After the initial medication reconciliation the investigators will review the participant's medications with pharmacy to determine if any significant drug-drug interactions exist between the participant's medications and D-Cycloserine. If such interactions are discovered the investigators will collaborate with the participant's prescribing physician to determine if dose alterations/discontinuation would benefit the participant while receiving D-Cycloserine therapy. For subsequent medication reconciliations at follow up visits the investigators will do the same for any new medications that the participant may be taking.
After clinical assessments, the investigators will routinely return results to the participant by phone or by secure messaging in the EMR (per standard clinical protocol).
In addition to the scheduled study visits the participant is encouraged to follow up with the the investigators via phone or by secure messaging in the EMR should they have any questions or updates about interval changes in the participant's clinical status. Each report will be assessed by the investigators and based on their clinical judgement the participant may require additional follow up evaluations.
If the results are acceptable and there is no contraindication to treatment the investigators will begin dosing D-Cycloserine following the baseline visit.
The D-Cycloserine (250 mg) capsules will be compounded to a suspension of 25 mg/mL, and for a starting dose the participant would take 15 mg/kg (253 mg = 10.1 mL) by mouth once daily. Throughout the study, based on serial clinical evaluations, sphingolipid levels, and toxicity monitoring the investigators will adjust the dose between 15-20 mg/kg/day at the discretion of the Principle Investigator (PI). The PI reserves the right to stop, temporarily hold, or adjust the dose of the medication at their discretion. As the participant grows and gains weight the investigators will adjust the dose as necessary in order to keep it at the goal of 15 to 20 mg/kg/day.
The time to peak concentration for D-cycloserine is 4 to 8 hours with a half-life elimination (with normal renal function) of 12 hours. Studies in pediatric patients recommend targeting serum concentrations of 25 to 30 mcg/mL to minimize neurotoxicity. Therefore ~6 hours after initial administration the investigators would draw a D-Cycloserine level to best understand the peak concentration obtained in the participant.
Given that concomitant pyridoxine is recommended to prevent cycloserine-induced neuropathy, at the time of D-Cycloserine initiation the investigators would also plan to supplement with pyridoxine. The pyridoxine (50 mg) tablets will be compounded to a suspension of 50 mg/mL, and the participant will take 0.4 mL (20 mg = approximately 1.18 mg/kg) by mouth once daily. If there is ongoing concern for drug related neuropathy at this starting dose then pyridoxine dose adjustments can be made towards a max of 2 mg/kg/day.
The schedule of assessments will be followed as long as the participant tolerates the treatment and continues to do well clinically. If there are concerns for tolerability, adverse events, or serious adverse events, at their discretion the PI reserves the right to stop, temporarily hold, or adjust the dose of the medication as well as increase the frequency of follow up assessments.
Weekly assessments will be conducted by the investigators to assess outcomes measures for the four weeks following the baseline visit. Following this period, outcome measures will be assessed every two weeks for a period of 8 weeks. Afterwards, pending reassuring data and lack of contraindications the investigators will space out assessments to once a month. At the 6 month interval assessment, a repeat MRI and Lumbar Puncture will be performed. Visits will continue monthly until 1 year post-baseline. A final MRI and Lumbar Puncture will be performed at the 1 year interval visit.
- Conditions
- Hereditary Spastic Paraplegia
- Being tested
- D-cycloserine
- Keywords
- D-Cycloserine, SPTSSA Gene, Complex Hereditary Spastic Paraplegia
- Medical subject headings
- Spastic Paraplegia, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-cycloserineDrug
Pyridoxine also prescribed to help prevent neurologic adverse events related to D-Cycloserine.
| Study group | Role | What they receive |
|---|---|---|
| D-Cycloserine | Experimental | D-Cycloserine Administered for Complex Hereditary Spastic Paraplegia Receives: Drug: D-cycloserine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of treatment related serious adverse event
Frequency of treatment related serious adverse events as assessed by CTCAE Version 5.0
Measured: From baseline to the end of treatment at 1 year
Concentration of D-Cycloserine
Concentration of D-Cycloserine in mcg/mL from serum blood samples drawn 6 hours after dosing
Measured: From baseline to the end of treatment at 1 year
Increases in serum AST and ALT in (U/L)
Measured: From baseline to the end of treatment at 1 year
Presence or Absence of Changes in Brain Magnetic Resonance Imaging
Changes in Brain Magnetic Resonance Imaging associated with adverse events
Measured: From baseline to the end of treatment at 1 year
Presence or Absence of Changes in Spine Magnetic Resonance Imaging
Change in Spine Magnetic Resonance Imaging associated with adverse events
Measured: From baseline to the end of treatment at 1 year
Presence or Absence of Changes in Electroencephalogram (EEG)
Changes in Electroencephalogram (EEG) associated with adverse events
Measured: From baseline to the end of treatment at 1 year
Presence or Absence of Changes on audiogram.
Changes in audiogram associated with adverse events related to hearing loss
Measured: From baseline to the end of treatment at 1 year
Presence of Absence of Changes in nerve conduction studies.
Changes in nerve conduction studies related to adverse events
Measured: From baseline to the end of treatment at 1 year
Presence or Absence of Changes in cognitive profile on neuropsychological testing.
Changes in neuropsychological testing related to adverse events
Measured: From baseline to the end of treatment at 1 year
Changes in gross motor function as measured by the Gross Motor Function Measure (GMFM-88)
Higher scores indicate better capacity for gross motor function
Measured: From baseline to the end of treatment at 1 year
Changes in spasticity as measured by findings on the Tardieu Spasticity Scale
That Tardieu Spasticity Scale is scored from 0 to 5. Lower scores are given for less spasticity while higher scores are given for more spasticity
Measured: From baseline to the end of treatment at 1 year
Changes in performance as measured by scores on Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)
Measured: From baseline to the end of treatment at 1 year
Secondary outcomes (2)
Decrease in sphingolipid levels
Decrease in sphingolipid levels in blood and CSF, targeted to be maintained at ~50% of pre-treatment levels
Measured: From baseline to the end of treatment at 1 year
Decrease in serum neurofilament light chain level
Decrease in serum neurofilament light chain level (pg/mL), targeted to be maintained at ~50% of pre-treatment levels
Measured: From baseline to the end of treatment at 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2026
- Study start10 Jul 2024
- Primary completion17 Mar 2026
- Study completion17 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Spastic ParaplegiaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- The treatment is already FDA approved for other indications (Tuberculosis and UTIs), and is being used off-label.
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Uniformed Services University of the Health Sciences, National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Principal investigator, Florian Eichler, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07542548
- Sponsor's protocol ID
- 2024P001068
- Other IDs
- 5T32GM007748-47, GR0235874
- Status last verified
- Apr 2026
- First submitted
- 4 Mar 2026
- Last updated
- 21 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: This is a single participant study. All IPD that underlie results in a publication will be shared
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- D-Cycloserine for Serine Palmitoyltransferase Inhibition: Treatment of a Single Patient With a Complex Hereditary Spastic Paraplegia Due to a De Novo Variant in the SPTSSA Gene
- ClinicalTrials.gov ID
- NCT07542548
- Acronym / sponsor ID
- 2024P001068
- Conditions
- Hereditary Spastic Paraplegia
- Keywords
- D-Cycloserine, SPTSSA Gene, Complex Hereditary Spastic Paraplegia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Uniformed Services University of the Health Sciences, National Institute of General Medical Sciences (NIGMS)
- Study start
- 10 Jul 2024 (actual)
- Primary completion
- 17 Mar 2026 (actual)
- Study completion
- 17 Mar 2026 (actual)
- First posted
- 21 Apr 2026 (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.
The overarching objective of this study is to mitigate the neurological decline associated with SPTSSA related Complex Hereditary Spastic Paraplegia
Detailed description
At each visit a medication reconciliation will be performed which will include medications, vitamins, herbal preparations, and supplements. For each medication the investigators will record start and end dates of administration, dosage, frequency, and reason for use. After the initial medication reconciliation the investigators will review the participant's medications with pharmacy to determine if any significant drug-drug interactions exist between the participant's medications and D-Cycloserine. If such interactions are discovered the investigators will collaborate with the participant's prescribing physician to determine if dose alterations/discontinuation would benefit the participant while receiving D-Cycloserine therapy. For subsequent medication reconciliations at follow up visits the investigators will do the same for any new medications that the participant may be taking.
After clinical assessments, the investigators will routinely return results to the participant by phone or by secure messaging in the EMR (per standard clinical protocol).
In addition to the scheduled study visits the participant is encouraged to follow up with the the investigators via phone or by secure messaging in the EMR should they have any questions or updates about interval changes in the participant's clinical status. Each report will be assessed by the investigators and based on their clinical judgement the participant may require additional follow up evaluations.
If the results are acceptable and there is no contraindication to treatment the investigators will begin dosing D-Cycloserine following the baseline visit.
The D-Cycloserine (250 mg) capsules will be compounded to a suspension of 25 mg/mL, and for a starting dose the participant would take 15 mg/kg (253 mg = 10.1 mL) by mouth once daily. Throughout the study, based on serial clinical evaluations, sphingolipid levels, and toxicity monitoring the investigators will adjust the dose between 15-20 mg/kg/day at the discretion of the Principle Investigator (PI). The PI reserves the right to stop, temporarily hold, or adjust the dose of the medication at their discretion. As the participant grows and gains weight the investigators will adjust the dose as necessary in order to keep it at the goal of 15 to 20 mg/kg/day.
The time to peak concentration for D-cycloserine is 4 to 8 hours with a half-life elimination (with normal renal function) of 12 hours. Studies in pediatric patients recommend targeting serum concentrations of 25 to 30 mcg/mL to minimize neurotoxicity. Therefore ~6 hours after initial administration the investigators would draw a D-Cycloserine level to best understand the peak concentration obtained in the participant.
Given that concomitant pyridoxine is recommended to prevent cycloserine-induced neuropathy, at the time of D-Cycloserine initiation the investigators would also plan to supplement with pyridoxine. The pyridoxine (50 mg) tablets will be compounded to a suspension of 50 mg/mL, and the participant will take 0.4 mL (20 mg = approximately 1.18 mg/kg) by mouth once daily. If there is ongoing concern for drug related neuropathy at this starting dose then pyridoxine dose adjustments can be made towards a max of 2 mg/kg/day.
The schedule of assessments will be followed as long as the participant tolerates the treatment and continues to do well clinically. If there are concerns for tolerability, adverse events, or serious adverse events, at their discretion the PI reserves the right to stop, temporarily hold, or adjust the dose of the medication as well as increase the frequency of follow up assessments.
Weekly assessments will be conducted by the investigators to assess outcomes measures for the four weeks following the baseline visit. Following this period, outcome measures will be assessed every two weeks for a period of 8 weeks. Afterwards, pending reassuring data and lack of contraindications the investigators will space out assessments to once a month. At the 6 month interval assessment, a repeat MRI and Lumbar Puncture will be performed. Visits will continue monthly until 1 year post-baseline. A final MRI and Lumbar Puncture will be performed at the 1 year interval visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The treatment is already FDA approved for other indications (Tuberculosis and UTIs), and is being used off-label.
| Arm | Type | Receives |
|---|---|---|
| D-Cycloserine | Experimental | Drug: D-cycloserineD-Cycloserine Administered for Complex Hereditary Spastic Paraplegia |
Who may qualify
- Ages
- 6 to 6 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- • Informed consent provided by the participant's parents.
Key exclusion criteria (3 listed)
- • Participant has any known contraindication to or unwillingness to undergo procedures listed in the protocol
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 |
|---|---|---|
| D-cycloserinePyridoxine also prescribed to help prevent neurologic adverse events related to D-Cycloserine. | Drug | D-Cycloserine |
Primary outcome
Frequency of treatment related serious adverse event
Time frame: From baseline to the end of treatment at 1 year
Frequency of treatment related serious adverse events as assessed by CTCAE Version 5.0
Concentration of D-Cycloserine
Time frame: From baseline to the end of treatment at 1 year
Concentration of D-Cycloserine in mcg/mL from serum blood samples drawn 6 hours after dosing
Increases in serum AST and ALT in (U/L)
Time frame: From baseline to the end of treatment at 1 year
Presence or Absence of Changes in Brain Magnetic Resonance Imaging
Time frame: From baseline to the end of treatment at 1 year
Changes in Brain Magnetic Resonance Imaging associated with adverse events
Presence or Absence of Changes in Spine Magnetic Resonance Imaging
Time frame: From baseline to the end of treatment at 1 year
Change in Spine Magnetic Resonance Imaging associated with adverse events
Presence or Absence of Changes in Electroencephalogram (EEG)
Time frame: From baseline to the end of treatment at 1 year
Changes in Electroencephalogram (EEG) associated with adverse events
Presence or Absence of Changes on audiogram.
Time frame: From baseline to the end of treatment at 1 year
Changes in audiogram associated with adverse events related to hearing loss
Presence of Absence of Changes in nerve conduction studies.
Time frame: From baseline to the end of treatment at 1 year
Changes in nerve conduction studies related to adverse events
Presence or Absence of Changes in cognitive profile on neuropsychological testing.
Time frame: From baseline to the end of treatment at 1 year
Changes in neuropsychological testing related to adverse events
Changes in gross motor function as measured by the Gross Motor Function Measure (GMFM-88)
Time frame: From baseline to the end of treatment at 1 year
Higher scores indicate better capacity for gross motor function
Changes in spasticity as measured by findings on the Tardieu Spasticity Scale
Time frame: From baseline to the end of treatment at 1 year
That Tardieu Spasticity Scale is scored from 0 to 5. Lower scores are given for less spasticity while higher scores are given for more spasticity
Changes in performance as measured by scores on Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)
Time frame: From baseline to the end of treatment at 1 year
2 secondary outcomes
Decrease in sphingolipid levels
Time frame: From baseline to the end of treatment at 1 year
Decrease in serum neurofilament light chain level
Time frame: From baseline to the end of treatment at 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2026.
- Individual participant dataSharing planned: Yes. This is a single participant study. All IPD that underlie results in a publication will be shared
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing D-cycloserine in people with Hereditary Spastic Paraplegia, run by Massachusetts General Hospital at 1 site in United States.
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 3 inclusion and 3 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: finished, as of the sponsor's last update on 21 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of treatment related serious adverse event (time frame: From baseline to the end of treatment at 1 year). The study lists 12 primary outcomes in all. 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 21 Apr 2026.